Biophysical limits on athermal effects of RF and microwave radiation

Using biophysical criteria, I show that continuous radiofrequency (RF) and microwave radiation with intensity less than 10 mW/cm(2) are unlikely to affect physiology significantly through athermal mechanisms. Biological systems are fundamentally noisy on the molecular scale as a consequence of thermal agitation and are noisy macroscopically as a consequence of physiological functions and animal behavior. If electromagnetic fields are to significantly affect physiology, their direct physical effect must be greater than that from the ubiquitous endogenous noise. Using that criterion, I show that none of a set of interactions of weak fields, which I argue is nearly complete on dimensional grounds, can affect biology on the molecular scale. Moreover, I conclude that such weak fields are quite unlikely to generate significant effects in their interactions with larger biological elements such as cells. In the course of that analysis, I examine important special examples of electromagnetic interactions: "direct" interactions where biology is modified simply by the motion of charged elements generated by the electric field; resonance interactions; the effects of electrostrictive forces and induced dipole moments; and modifications of radical pair recombination probabilities. In each case, I show that it is unlikely that low intensity fields can generate significant physiological consequences.     

ELF Noise Fields: A Review

The debate as to whether low-level electromagnetic fields can affect biological systems and in the long term cause health effects has been going on for a long time. Yet the interaction of weak electromagnetic fields (EMF) with living cells, undoubtedly a most important phenomenon, is still not well understood. The exact mechanisms by which the effects are produced have not been identified. Furthermore, it is not possible to clearly define which aspects of an EMF exposure that constitute the “dose.” One of the groups that contributed to solving this problem is the Bioelectromagnetics group at Catholic University of America (CUA), Washington, D.C. Their work has been devoted to investigating the physical parameters that are needed to obtain an effect of EMF exposure on biological systems, and also how to inhibit the effect. This is a review of their work on bioeffects caused by low-level EMF, their dependence on coherence time, constancy, spatial averaging, and also how the effects can be modified by an applied ELF noise magnetic field. The group has been using early chick embryos, and L929 and Daudi cells as their main experimental systems. The review also covers the work of other groups on low-level effects and the inhibition of the effects with an applied noise field. The group at CUA has shown that biological effects can be found after exposure to low-level ELF and RF electromagnetic fields, and when effects are observed, applying an ELF magnetic noise field inhibits the effects. Also, other research groups have tried to replicate the studies from the CUA group, or to apply EMF noise to suppress EMF-induced effects. Replications of the CUA effects have not always been successful. However, in all cases where the noise field has been applied to prevent an observed effect, it has been successful in eliminating the effect.     

Bio-soliton model that predicts non-thermal electromagnetic frequency bands,that either stabilize or destabilize living cells

Solitons, as self-reinforcing solitary waves, interact with complex biological phenomena such as cellular self-organization. A soliton model is able to describe a spectrum of electromagnetism modalities that can be applied to understand the physical principles of biological effects in living cells, as caused by endogenous and exogenous electromagnetic fields and is compatible with quantum coherence. A bio-soliton model is proposed, that enables to predict which eigen-frequencies of non-thermal electromagnetic waves are life-sustaining and which are, in contrast, detrimental for living cells. The particular effects are exerted by a range of electromagnetic wave eigen-frequencies of one-tenth of a Hertz till Peta Hertz that show a pattern of 12 bands, and can be positioned on an acoustic reference frequency scale. The model was substantiated by a meta-analysis of 240 published articles of biological electromagnetic experiments, in which a spectrum of non-thermal electromagnetic waves were exposed to living cells and intact organisms. These data support the concept of coherent quantized electromagnetic states in living organisms and the theories of Fröhlich, Davydov and Pang. It is envisioned that a rational control of shape by soliton-waves and related to a morphogenetic field and parametric resonance provides positional information and cues to regulate organism-wide systems properties like anatomy, control of reproduction and repair.     

Contact response of cells can mediate morphogenetic pattern formation

Theories of morphogenetic pattern formation have included Turing's chemical prepatterns, mechanochemical interactions, cell sorting, and other mechanisms involving guided motion or signalling of cells. Many of these theories presuppose long-range cellular communication or other controls such as chemical concentration fields. However, the possibility that direct interactions between cells can lead to order and structure has not been seriously investigated in mathematical models. In this paper we consider this possibility, with emphasis on cells that reorient and align with each other when they come into contact. We show that such contact responses can account for the formation of multicellular patterns called parallel arrays. These patterns typically occur in tissue cultures of fibroblasts, and consist of clusters of cells sharing a common axis of orientation. Using predictions of a mathematical model and computer simulations of cell motion and interactions we show that contact responses alone, in the absence of other global controls, can promote the formation of these patterns. We suggest other situations in which patterns may result from direct cellular communication. Previous theories of morphogenesis are briefly reviewed and compared with this proposed mechanism.     

Sociality of an agent during morphogenetic canalization: Asynchronous updating with potential resonance

Canalization is a typical self-organization process leading to complementarity between parts and the whole. In the field of developmental biology, concerns about morphogenesis canalization are often framed as the French flag problem, questioning how each cell knows its own position in the whole system. Although chemical gradients have been suggested to provide positional information, there is no direct evidence that gradients are used to gain positional information. The chemical gradient hypothesis is based on the assumption that agents (e.g., cells) in a domain that locally interact with each other can generate a chemical gradient thanks to a global reference point. Instead of a chemical gradient, we here propose a model based on agents that are equipped with sociality that is based not on a global reference but rather on the ability to sense other neighboring agents, or potential resonance. The interaction among the agents with sociality, developed from undifferentiated types or tokens, is implemented using asynchronous updating automata equipped with potential resonance. We show that these automata can generate a French flag pattern that is very robust against perturbations without positional information by comparing automata with synchronous updating and asynchronous automata without potential resonance.     

Exposure to GSM RF Fields Does Not Affect Calcium Homeostasis in Human Endothelial Cells,Rat Pheocromocytoma Cells or Rat Hippocampal Neurons

In the course of modern daily life, individuals are exposed to numerous sources of electromagnetic radiation that are not present in the natural environment. The strength of the electromagnetic fields from sources such as hairdryers, computer display units and other electrical devices is modest. However, in many home and office environments, individuals can experience perpetual exposure to an “electromagnetic smog”, with occasional peaks of relatively high electromagnetic field intensity. This has led to concerns that such radiation can affect health. In particular, emissions from mobile phones or mobile phone masts have been invoked as a potential source of pathological electromagnetic radiation. Previous reports have suggested that cellular calcium (Ca²⁺) homeostasis is affected by the types of radiofrequency fields emitted by mobile phones. In the present study, we used a high-throughput imaging platform to monitor putative changes in cellular Ca²⁺ during exposure of cells to 900 MHz GSM fields of differing power (specific absorption rate 0.012–2 W/Kg), thus mimicking the type of radiation emitted by current mobile phone handsets. Data from cells experiencing the 900 Mhz GSM fields were compared with data obtained from paired experiments using continuous wave fields or no field. We employed three cell types (human endothelial cells, PC-12 neuroblastoma and primary hippocampal neurons) that have previously been suggested to be sensitive to radiofrequency fields. Experiments were designed to examine putative effects of radiofrequency fields on resting Ca²⁺, in addition to Ca²⁺ signals evoked by an InsP₃-generating agonist. Furthermore, we examined putative effects of radiofrequency field exposure on Ca²⁺ store emptying and store-operated Ca²⁺ entry following application of the Ca²⁺ATPase inhibitor thapsigargin. Multiple parameters (e.g., peak amplitude, integrated Ca²⁺ signal, recovery rates) were analysed to explore potential impact of radiofrequency field exposure on Ca²⁺ signals. Our data indicate that 900 MHz GSM fields do not affect either basal Ca²⁺ homeostasis or provoked Ca²⁺ signals. Even at the highest field strengths applied, which exceed typical phone exposure levels, we did not observe any changes in cellular Ca²⁺ signals. We conclude that under the conditions employed in our experiments, and using a highly-sensitive assay, we could not detect any consequence of RF exposure.     

Electromagnetic field effects on cells of the immune system: the role of calcium signaling.

During the past decade considerable evidence has accumulated demonstrating that nonthermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be relevant to in vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca(2+)-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca2+ in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca2+ signaling processes are involved in the mediation of field effects on the immune system.     

The physics and neurobiology of magnetoreception

Diverse animals can detect magnetic fields but little is known about how they do so. Three main hypotheses of magnetic field perception have been proposed. Electrosensitive marine fish might detect the Earth's field through electromagnetic induction, but direct evidence that induction underlies magnetoreception in such fish has not been obtained. Studies in other animals have provided evidence that is consistent with two other mechanisms: biogenic magnetite and chemical reactions that are modulated by weak magnetic fields. Despite recent advances, however, magnetoreceptors have not been identified with certainty in any animal, and the mode of transduction for the magnetic sense remains unknown.     

Temporal analysis of moving DC electric fields in aquatic media

Many aquatic vertebrates can sense the weak electric fields generated by other animals and may also sense geoelectric or electromagnetic phenomena for use in orientation. All these sources generate stationary (dc) fields. In addition, fields from animals are modulated by respiration and other body movements. Since electroreceptors are insensitive to a pure dc field, it has been suggested that the ac modulation carries most of the relevant information for electrosensory animals. However, in a natural situation pure dc fields are rare since any relative movement between source and receiver will transform a dc field into a time varying signal. In this paper, we will describe the properties of such signals and how they are filtered at the first stage of electrosensory information processing in the brain. We will show that the signal perceived by an animal traversing a dc electric field contains all the information necessary to reconstruct the distance to the source and that the signal conditioning algorithms are perfectly adapted to preserve such information.     

Cellular communication and coupling within the suprachiasmatic nucleus

In mammals, the part of the nervous system responsible for most circadian behavior can be localized to a pair of structures in the hypothalamus known as the suprachiasmatic nucleus (SCN). Importantly, when SCN neurons are removed from the organism and maintained in a brain slice preparation, they continue to generate 24h rhythms in electrical activity, secretion, and gene expression. Previous studies suggest that the basic mechanism responsible for the generation of these rhythms is intrinsic to individual cells in the SCN. If we assume that individual cells in the SCN are competent circadian oscillators, it is obviously important to understand how these cells communicate and remain synchronized with each other. Cell-to-cell communication is clearly necessary for conveying inputs to and outputs from the SCN and may be involved in ensuring the high precision of the observed rhythm. In addition, there is a growing body of evidence that a number of systems-level phenomena could be dependent on the cellular communication between circadian pacemaker neurons. It is not yet known how this cellular synchronization occurs, but it is likely that more than one of the already proposed mechanisms is utilized. The purpose of this review is to summarize briefly the possible mechanisms by which the oscillatory cells in the SCN communicate with each other. (Chronobiology International, 18(4)579-600, 2001)     

Primary processes in sensory cells: current advances

In the course of evolution, the strong and unremitting selective pressure on sensory performance has driven the acuity of sensory organs to its physical limits. As a consequence, the study of primary sensory processes illustrates impressively how far a physiological function can be improved if the survival of a species depends on it. Sensory cells that detect single-photons, single molecules, mechanical motions on a nanometer scale, or incredibly small fluctuations of electromagnetic fields have fascinated physiologists for a long time. It is a great challenge to understand the primary sensory processes on a molecular level. This review points out some important recent developments in the search for primary processes in sensory cells that mediate touch perception, hearing, vision, taste, olfaction, as well as the analysis of light polarization and the orientation in the Earth’s magnetic field. The data are screened for common transduction strategies and common transduction molecules, an aspect that may be helpful for researchers in the field.     

Involvement of ERK and protein tyrosine phosphatase signaling pathways in EGCG-induced cyclooxygenase-2 expression in Raw 264.7 cells

The cellular stress response which can be elicited by a variety of physical or chemical stressors challenges the homeostatic mechanisms of the cells. Two stressors may interact such that, for example, in the presence of a defined thermal stress ("costress") a second weak stressor like electromagnetic fields (50 MHz, 100 microT) produces strong biological effects. Based on the apparent interaction of these stressors a concept is suggested that explains the observed effects and defines the limits of cellular homeostasis in general terms. The homeostatic potential of a cell and hence the ability to cope with stressors can be altered by eliciting or depressing the heat shock response. This manipulation has several promising medical applications.     

Living matter—nexus of physics and biology in the 21st century

Cells are made up of complex assemblies of cytoskeletal proteins that facilitate force transmission from the molecular to cellular scale to regulate cell shape and force generation. The “living matter” formed by the cytoskeleton facilitates versatile and robust behaviors of cells, including their migration, adhesion, division, and morphology, that ultimately determine tissue architecture and mechanics. Elucidating the underlying physical principles of such living matter provides great opportunities in both biology and physics. For physicists, the cytoskeleton provides an exceptional toolbox to study materials far from equilibrium. For biologists, these studies will provide new understanding of how molecular-scale processes determine cell morphological changes.The distinction between being “alive” or “not alive” has been a long-standing question for those interested in our natural world. In many ancient cultures, the difference between living organisms and inorganic matter was thought to be due to innate differences arising from a “vital force,” such that biology operated with different fundamental properties than the physical world. The ability to disprove such theories came about over the course of the 17th to the 19th centuries, as scientists developed theories of atoms and were able to synthesize organic matter from inorganic constituents. Over the past 100 years, developments in molecular biology and biochemistry have provided a wealth of information on the structure and function of biological molecules, much of which was acquired in collaborations between physical and biological scientists. Application of X-ray–scattering techniques first developed to study metals enabled discovery of the structure of complicated biological molecules ranging from DNA to ion channels. Use of laser trapping techniques first developed to trap and cool atoms enabled precise force spectroscopy measurements of single molecular motors. We now know that biological molecules, while more complicated than their inorganic counterparts, must obey the rules of physics and chemistry.This wealth of molecular-scale information does not directly inform the behaviors of living cells. The organelles within cells are made up of complex and dynamic assemblies of proteins, lipids, and nucleic acids, all immersed within an aqueous environment. These assemblies are somehow able to build materials that can robustly facilitate the plethora of morphological and physical behaviors of cells at the subcellular (intracellular transport), cellular (division, adhesion, migration), and multicellular (tissue morphogenesis, wound healing) length scales. The dynamic cytoskeleton transmits information and forces from the molecular to the cellular length scales. But what is it about the behaviors of biological molecules that endow cells with the ability to respirate, move, and replicate themselves robustly—all qualities we consider essential to “life”? For these questions, understanding of the physics and chemistry of systems of biological molecules is needed. Interactions that occur within ensembles of molecules lead to emergent properties and behaviors that cannot be predicted at the single-molecule level. These emergent chemical and physical properties of living matter are likely fundamentally different from inorganic or “dead” materials. Discovering the underlying principles of living matter provides fantastic opportunities to learn new physics and biology.The fields of condensed matter physics and materials science study the physical properties that emerge when objects (e.g., atoms, molecules, grains of sand, or soap bubbles) are placed in sufficiently close proximity, such that interactions between them cannot be ignored. Interatomic or intermolecular interactions give rise to emergent properties that are not seen in isolated species. Familiar examples involve electron transport across a material or a material''s response to externally applied magnetic fields or mechanical forces. These emergent properties, such as conductivity, elasticity, and viscosity, enable us to predict the behavior of a collection of objects in these condensed phases. In this paper, I will focus on my perspective of how approaches to understanding the mechanical properties of physical materials can inform understanding of the mechanical properties of living matter found within cells.In a crystal of metal, precisely organized atoms are located nanometers apart, and the energies of their interactions are on the scale of an electron volt (40-fold larger than thermal energy or twice the energy released on the hydrolysis of a single ATP molecule). These give rise to an energy density, or elastic modulus, on the order of gigapascals, which underlies the rigidity of metals. For small deformations, the restoring force between atoms means that this metal behaves like an elastic spring: after a force is applied, the metal returns to its original shape. Understanding force transmission through crystalline metals was facilitated by the development of elasticity theory in the 16th and 17th centuries. Fluids, such as water, lack crystalline order, but predictive understanding of fluid flows and forces was captured through development of theories of fluid dynamics. Now think of another material, Silly Putty, which behaves elastically at short timescales (it bounces like a rubber ball) but then oozes and flows at long timescales, acting like a viscous fluid. Silly Putty is made of long polymers that are trapped by one another at short timescales, but thermal energy is sufficient to allow them to diffuse and translocate at long timescales. Silly Putty is also a “soft material,” in that the polymer''s interaction energies are at the thermal energy level, and its length scale is at the micrometer level. Materials like Silly Putty were thought to be too complicated for analytical theory. It was only in the middle of the 20th century that the theoretical framework to understand these “messy” and “disorganized” polymer-based materials was developed.The most powerful theories for understanding these vastly different forms of physical matter were developed in the absence of even the simplest of computers. The theories relied on developing physical properties or parameters to describe the material with a “mean field,” a type of coarse-graining that identifies the essential properties of individual constituents and interactions but ignores many other details. These mean fields give us new intuitions concerning the origin of material properties and give rise to definitions of physical parameters, such as elasticity and viscosity. However, these theories also require materials that do not jostle around a lot and remain close to equilibrium. In fact, understanding materials “far from equilibrium” has been identified as a major challenge in physics for the next century (National Research Council, 2007) .Materials formed by dynamic protein assemblies in the cytoskeleton are disorganized, heterogeneous, and driven far from equilibrium. Motor proteins generate local stresses, and their activity is spatially modulated. The polymerization and depolymerization of cytoskeletal polymers is controlled by a myriad of regulatory proteins. All these dynamic molecular processes endow the cytoskeletal assemblies with unique behaviors that enable them to support complex physiological tasks. It is likely these dynamics also provide underlying robustness of the cells in response to fluctuating and changing environments. These properties make living cells exquisite materials that cannot be captured by existing frameworks of physical matter. I suspect that we have not yet identified the important parameters needed to characterize their properties. The rich dynamics created by active biological matter present a formidable challenge in the area of materials science.How do we hope to understand the properties of these complex cytoskeletal assemblies and materials? It may seem as though understanding cytoskeletal machinery is an insurmountable feat, the approaches that have been successful for physical materials will not work, and we must rely on complex simulations that require modeling of all individual components. This may be true. However, I think that this is a pessimistic view. Just consider how complicated physical materials would be if we did not have the appropriate parameters to describe the macroscopic responses and had instead became obsessed about knowing the details of all the interactions between underlying atoms and molecules? In the same vein, I believe that predictive insights into biological matter will emerge through development of new physical theories that use mean-field approaches to understanding materials that contain active components and are driven far from equilibrium. The burgeoning field of active-matter physics is currently considering these questions (Ramaswamy, 2010) . However, these theoretical approaches require physical measurements of cells and cellular proteins that may not be clearly linked to a physiological process or have a clear biological context. Materials built from cytoskeletal proteins in vitro should also provide an excellent source of experimental measurements, but closer collaboration with theorists working in this field and collaboration between biochemists and experimental physical scientists is needed to develop control over such materials. Developing predictive physical theories of the cytoskeleton will elucidate principles of why “the whole is more than the sum of its parts” that will provide greater control and design over living matter, in the same way that engineering has provided great advances in applications of materials from the physical world.What do biologists gain from theories of living matter? These theories will provide a crucial link between molecular and cellular length scale behaviors and will provide insight into the mechanisms of why specific molecular perturbations alter cell behavior. Moreover, they should provide us with general design principles of living matter. What are the basic aspects of a machine needed to separate chromosomes, establish polarity, or generate contractile forces that is utilized across different cell types? Can knowing these aspects provide insight into the evolution of cellular machines and the robustness of cell behavior? Thus, study of cellular materials both provides new opportunities for physicists and will provide crucial predictive understanding of cell physiology.Open in a separate windowMargaret L. Gardel     

CELLULAR COMMUNICATION AND COUPLING WITHIN THE SUPRACHIASMATIC NUCLEUS

In mammals, the part of the nervous system responsible for most circadian behavior can be localized to a pair of structures in the hypothalamus known as the suprachiasmatic nucleus (SCN). Importantly, when SCN neurons are removed from the organism and maintained in a brain slice preparation, they continue to generate 24h rhythms in electrical activity, secretion, and gene expression. Previous studies suggest that the basic mechanism responsible for the generation of these rhythms is intrinsic to individual cells in the SCN. If we assume that individual cells in the SCN are competent circadian oscillators, it is obviously important to understand how these cells communicate and remain synchronized with each other. Cell-to-cell communication is clearly necessary for conveying inputs to and outputs from the SCN and may be involved in ensuring the high precision of the observed rhythm. In addition, there is a growing body of evidence that a number of systems-level phenomena could be dependent on the cellular communication between circadian pacemaker neurons. It is not yet known how this cellular synchronization occurs, but it is likely that more than one of the already proposed mechanisms is utilized. The purpose of this review is to summarize briefly the possible mechanisms by which the oscillatory cells in the SCN communicate with each other. (Chronobiology International, 18(4)579–600, 2001)     

Evolution of research on cellular motility over five decades

This short review traces how our knowledge of the molecular mechanisms of cellular movements originated and developed over the past 50 years. Work on actin-based and microtubule-based movements developed in different ways, but in both fields, the discovery of the key proteins drove progress. Starting from an inventory of zero molecules in 1960, both fields matured spectacularly, so we now know the atomic structures of the important proteins, understand the kinetics and thermodynamics of their interactions, have documented how the molecules behave in cells, and can test theories with molecularly explicit computer simulations of cellular processes.     

Hyphal and mycelial consciousness: the concept of the fungal mind

Like other cells, fungal hyphae show exquisite sensitivity to their environment. This reactiveness is demonstrated at many levels, from changes in the form of the hypha resulting from alterations in patterns of exocytosis, to membrane excitation, and mechanisms of wound repair. Growing hyphae detect ridges on surfaces and respond to restrictions in their physical space. These are expressions of cellular consciousness. Fungal mycelia show decision-making and alter their developmental patterns in response to interactions with other organisms. Mycelia may even be capable of spatial recognition and learning coupled with a facility for short-term memory. Now is a fruitful time to recognize the study of fungal ethology as a distinctive discipline within mycology.     

Computational models of signalling networks for non-linear control

Artificial signalling networks (ASNs) are a computational approach inspired by the signalling processes inside cells that decode outside environmental information. Using evolutionary algorithms to induce complex behaviours, we show how chaotic dynamics in a conservative dynamical system can be controlled. Such dynamics are of particular interest as they mimic the inherent complexity of non-linear physical systems in the real world. Considering the main biological interpretations of cellular signalling, in which complex behaviours and robust cellular responses emerge from the interaction of multiple pathways, we introduce two ASN representations: a stand-alone ASN and a coupled ASN. In particular we note how sophisticated cellular communication mechanisms can lead to effective controllers, where complicated problems can be divided into smaller and independent tasks.     

Effects of extremely low frequency (50 Hz) magnetic field on morphological and biochemical properties of human keratinocytes

We investigated the effects on human keratinocytes (HaCaT) of exposure to a sinusoidal magnetic field of 2 mT (50 Hz). These cells are a good model for studying interaction of nonionising radiation, because they are not shielded from fields in vivo and also because they are resistant to both mechanical and thermal stimuli. We performed scanning microscopy which showed modification in shape and morphology in exposed cells. This modification is related to differential actin distribution as revealed by phalloidin fluorescence analysis. Moreover, the exposed cells show increased clonogenic capacity, as well as increased cellular growth as showed by clonogenicity assays and growth curves. Indirect immunofluorescence analysis using a fluorescent antibody against involucrin and beta4 integrin, which are respectively differentiation and adhesion markers, revealed an increase of involucrin expression and segregation of beta4 integrin in the cell membrane in cells exposed to 50 Hz; a higher percentage of the exposed cells shows a modified pattern of adhesion and differentiation markers. We also present evidence that exposure of HaCaT cells can interfere with protein kinase activity. Our observations confirm the hypothesis that electromagnetic fields at 50 Hz may modify cell membrane morphology and interfere with initiation of the signal cascade pathway and cellular adhesion.     

Dosage suppression genetic interaction networks enhance functional wiring diagrams of the cell

Dosage suppression is a genetic interaction in which overproduction of one gene rescues a mutant phenotype of another gene. Although dosage suppression is known to map functional connections among genes, the extent to which it might illuminate global cellular functions is unclear. Here we analyze a network of interactions linking dosage suppressors to 437 essential genes in yeast. For 424 genes, we curated interactions from the literature. Analyses revealed that many dosage suppression interactions occur between functionally related genes and that the majority do not overlap with other types of genetic or physical interactions. To confirm the generality of these network properties, we experimentally identified dosage suppressors for 29 genes from pooled populations of temperature-sensitive mutant cells transformed with a high-copy molecular-barcoded open reading frame library, MoBY-ORF 2.0. We classified 87% of the 1,640 total interactions into four general types of suppression mechanisms, which provided insight into their relative frequencies. This work suggests that integrating the results of dosage suppression studies with other interaction networks could generate insights into the functional wiring diagram of a cell.