Biophysics of α-synuclein membrane interactions

Membrane proteins participate in nearly all cellular processes; however, because of experimental limitations, their characterization lags far behind that of soluble proteins. Peripheral membrane proteins are particularly challenging to study because of their inherent propensity to adopt multiple and/or transient conformations in solution and upon membrane association. In this review, we summarize useful biophysical techniques for the study of peripheral membrane proteins and their application in the characterization of the membrane interactions of the natively unfolded and Parkinson's disease (PD) related protein, α-synuclein (α-syn). We give particular focus to studies that have led to the current understanding of membrane-bound α-syn structure and the elucidation of specific membrane properties that affect α-syn-membrane binding. Finally, we discuss biophysical evidence supporting a key role for membranes and α-syn in PD pathogenesis. This article is part of a Special Issue entitled: Membrane protein structure and function.     

Biophysics; fifty years after Schrödinger

E. Schrödinger described his mechanistic view on life in his book “What is Life?” published in 1944. H. Yukawa stated that life is like a building of bricks. Is life understandable in this manner?In 1950–1960 the generation of structure and function in living cells was shown to be analyzable, step by step, within the theoretical framework of physics. In the 1970's the concept of a molecular machine or unit machine in living cells was clearly presented and the effort to experimentally define unit machines was promoted. Recently, new techniques to directly observe their behaviors have been developed. The machines are not always rigid. In sliding machines, the influx-efflux coupling has been found to be loose. For loose coupling, intramachine flexibility seems to be useful.Living cells can be regarded as an organized system composed of many unit machines, some of which exhibit deterministic behaviors while others exhibit probabilistic behaviors. The cells do not always show a definite response to a given input. We need new statistical mechanics for the study of unit machines and their systems which have complex spatial and temporal structures. They may have a mechanism beyond a simple building of bricks.     

Culinary Biophysics: on the Nature of the 6X??C Egg

Shell-on eggs cooked by immersion in water at low and constant temperatures (∼60–70 °C) yield yolks with very particular textures. Structure development in such unique cooking conditions is far from understood. The present study shows that egg yolk, despite its compositional complexity, follows typical gelation kinetics found in many globular proteins and that it can develop structure at temperatures as low as 56 °C. It follows that yolk texture is dictated by time/temperature combinations. Under isothermal, low temperature cooking conditions, the thickening and gelation kinetics of egg yolk follow Arrhenius-type kinetic relationships. The energy of activation of these processes was ∼470 kJ mol⁻¹, which agrees well with the values reported for the denaturation and gelation of the thermally labile chicken serum albumin and immunoglobulin Y. Results are related to common foodstuffs in order to allow chefs and home cooks to achieve a priori conceived textures in egg yolks.     

Biophysics of endocytic vesicle formation: A focus on liquid–liquid phase separation

Endocytosis is a fine-tuned mechanism of cellular communication through which cells internalize molecules on the plasma membrane, such as receptors and their bound ligands. Through receptor clustering in endocytic pits, recruitment of active receptors to different endocytic routes and their trafficking towards different fates, endocytosis modulates cell signaling and ultimately leads to a variety of biological responses. Many studies have focused their attention on specialized endocytic mechanisms depending on the nature of the internalizing cargo and cellular context, distinct sets of coat proteins, endocytic adaptors and membrane lipids. Here, we review recent advances in our understanding of the principles underlying endocytic vesicle formation, integrating both biochemical and biophysical factors, with a particular focus on intrinsically disordered regions (IDRs) creating weakly interconnected protein networks assembled through liquid–liquid phase separation (LLPS) and driving membrane bending especially in clathrin-mediated endocytosis (CME). We finally discuss how these properties impinge on receptor fate and signaling.     

How do we Measure the Environment? Linking Intertidal Thermal Physiology and Ecology Through Biophysics

Recent advances in quantifying biochemical and cellular-levelresponses to thermal stress have facilitated a new explorationof the role of climate and climate change in driving intertidalcommunity and population ecology. To fruitfully connect thesedisciplines, we first need to understand what the body temperaturesof intertidal organisms are under field conditions, and howthey change in space and time. Newly available data logger technologymakes such an exploration possible, but several potential pitfallsmust be avoided. Body temperature during aerial exposure isdriven by multiple, interacting climatic factors, and extremesduring low tide far exceed those during submersion. Moreover,because of effects of body size and morphology, two organismsexposed to identical climatic conditions can display very differentbody temperatures, which can also be substantially differentfrom the temperature of the surrounding air. These same factorsdrive the temperature recorded by data loggers, and one loggertype is unlikely to serve as an effective proxy for all organismsat a site. Here I describe the difficulties involved in quantifyingpatterns of body temperature in intertidal organisms, and explorethe implications of this complexity for intertidal physiologicalecology. I do so using data from temperature loggers designedto mimic the thermal characteristics of the mussel Mytilus californianus,and deployed at multiple sites along the West Coast of the UnitedStates. Results indicate a highly intricate pattern of thermalstress, where the interaction of climate with the dynamics ofthe tidal cycle determines the timing and magnitude of temperatureextremes, creating a unique "thermal signal" at each site.     

Adriano Buzzati-Traverso and the foundation of the International Laboratory of Genetics and Biophysics in Naples (1962–1969)

Despite a long tradition of research in applied genetics, particularly in agricultural research, in Italy the transition to the new knowledges and techniques of molecular biology was long and difficult. Political and financial constraints made academic institutions very slow to grasp the importance of molecular approaches to biology and medicine. In fact, the main studies concerning problems of molecular biology took place inside non-academic institutions. We reconstruct the complex paths leading to the birth of the International Laboratory of Genetics and Biophysics (LIGB) in Naples, and describe its work and activities in the period in which it was directed by its creator, Adriano Buzzati-Traverso, between 1962 and 1969. The origins of the LIGB are inextricably bound to the growth of biophysical research at the University of Pavia and at the Higher Health Institute in Rome. For a short period, with the aid provided by Italian and European physicists to biological research on the effects of nuclear radiation, LIGB became a focal point in European molecular biology. In 1968 the scientific and educational activities of the LIGB dramatically fell victim to the contradictions of the Italian academic and scientific system, and to the political climate which emerged in Italy at the time.