Integrins in cell migration

Integrin-based adhesion has served as a model for studying the central role of adhesion in migration. In this article, we outline modes of migration, both integrin-dependent and -independent in vitro and in vivo. We next discuss the roles of adhesion contacts as signaling centers and linkages between the ECM and actin that allows adhesions to serve as traction sites. This includes signaling complexes that regulate migration and the interplay among adhesion, signaling, and pliability of the substratum. Finally, we address mechanisms of adhesion assembly and disassembly and the role of adhesion in cellular polarity.     

Recap on cell migration

Most animal cells move cross-linked surface antigens to one pole of the cell, a phenomenon called 'capping'. It is closely related to the rearward movement of particles attached to their surface. Cap formation is one of the most accessible dynamic properties of cells and is closely related to how they move. Yet, how this occurs is unknown.     

An in vitro model of cell migration: evaluation of vascular endothelial cell migration

In vivo vascular endothelial cell (VEC) migration is thought to play a central role in the development of new capillaries as well as the resurfacing of large vessels. Recently, we have developed an in vitro VEC migration assay system based on the ability of VEC to migrate off of tissue culture microcarrier beads. For these studies, bovine pulmonary artery VEC were grown to confluence on Cytodex 3 microcarrier beads (MCB). Next, the confluent VEC covered microcarrier beads were pipetted into 4-cm2 wells of a tissue culture plate and incubated at 37 degrees C/5% CO2. At various time intervals, the movement of the VEC off of the MCB onto the tissue culture surface was evaluated microscopically. Using this assay, we have studied the effect of endothelial cell growth supplement and various matrices (i.e., fibronectin, gelatin, and Matrigel) on VEC migration. These studies demonstrated that: (i) gelatin had no effect on normal or mitomycin C-pretreated VEC migration; (ii) fibronectin had no effect on normal VEC migration, but stimulated the relative migration of mitomycin pretreated VEC; and (iii) Matrigel significantly suppressed both normal and mitomycin C-pretreated VEC migration. Endothelial cell growth supplement (ECGS) stimulated both normal and mitomycin C-pretreated VEC migration on fibronectin at concentrations of 10 micrograms/ml ECGS. Pretreatment with ECGS had no effect of normal or mitomycin C VEC migration on gelatin. Finally, ECGS stimulated a statistically significant increase in the migration of normal and mitomycin C-pretreated VEC migration on Matrigel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Imaging developmental cell cycles

The last decade has seen a major expansion in development of live biosensors, the tools needed to genetically encode them into model organisms, and the microscopic techniques used to visualize them. When combined, these offer us powerful tools with which to make fundamental discoveries about complex biological processes. In this review, we summarize the availability of biosensors to visualize an essential cellular process, the cell cycle, and the techniques for single-cell tracking and quantification of these reporters. We also highlight studies investigating the connection of cellular behavior to the cell cycle, particularly through live imaging, and anticipate exciting discoveries with the combination of these technologies in developmental contexts.     

Nuclear mechanics during cell migration

During cell migration, the movement of the nucleus must be coordinated with the cytoskeletal dynamics at the leading edge and trailing end, and, as a result, undergoes complex changes in position and shape, which in turn affects cell polarity, shape, and migration efficiency. We here describe the steps of nuclear positioning and deformation during cell polarization and migration, focusing on migration through three-dimensional matrices. We discuss molecular components that govern nuclear shape and stiffness, and review how nuclear dynamics are connected to and controlled by the actin, tubulin and intermediate cytoskeleton-based migration machinery and how this regulation is altered in pathological conditions. Understanding the regulation of nuclear biomechanics has important implications for cell migration during tissue regeneration, immune defence and cancer.     

Endosomal signaling and cell migration

Cell migration is a complex biological process that is under the tight control of diverse signaling events. While many of the involved signaling molecules diffuse rapidly within cells, it now seems that certain key regulators of cell migration prefer to travel on endosomes. In this review we will discuss the multiple roles of signaling endosomes in regulation of local migration stimuli, dynamics of focal adhesions, cell contractility and locomotion.     

Collective migration and cell jamming

Our traditional physical picture holds with the intuitive notion that each individual cell comprising the cellular collective senses signals or gradients and then mobilizes physical forces in response. Those forces, in turn, drive local cellular motions from which collective cellular migrations emerge. Although it does not account for spontaneous noisy fluctuations that can be quite large, the tacit assumption has been one of linear causality in which systematic local motions, on average, are the shadow of local forces, and these local forces are the shadow of the local signals. New lines of evidence now suggest a rather different physical picture in which dominant mechanical events may not be local, the cascade of mechanical causality may be not so linear, and, surprisingly, the fluctuations may not be noise as much as they are an essential feature of mechanism. Here we argue for a novel synthesis in which fluctuations and non-local cooperative events that typify the cellular collective might be illuminated by the unifying concept of cell jamming. Jamming has the potential to pull together diverse factors that are already known to contribute but previously had been considered for the most part as acting separately and independently. These include cellular crowding, intercellular force transmission, cadherin-dependent cell–cell adhesion, integrin-dependent cell–substrate adhesion, myosin-dependent motile force and contractility, actin-dependent deformability, proliferation, compression and stretch.     

Calcium gradients underlying cell migration

The calcium ion is the simplest and most versatile second messenger in biology. Harboring a myriad of calcium effector proteins, migrating cells display an exquisite multiscaled and multilayered architecture of intracellular calcium dynamics. In motile fibroblasts, for instance, there are transient calcium microdomains ('calcium flickers') of ~5 μm in diameter and 10-2000 ms in duration, a rising flicker activity gradient along the rear-to-front axis, and a shallow background calcium concentration gradient in the opposite direction. When subjected to external gradients of guidance cues, local flicker gradients are created de novo in the leading edge, which steer cells to turn in new directions as defined by the asymmetry of the flicker activity, apparently by a stochastic decision-making mechanism. These recent findings provide a glimpse into how spatiotemporally coordinated calcium gradients orchestrate cellular behavior as complex as directional movement.     

Mechanotransduction in endothelial cell migration

The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. EC migration can be regulated by different mechanisms such as chemotaxis, haptotaxis, and mechanotaxis. This review will focus on fluid shear stress-induced mechanotransduction during EC migration. EC migration and mechanotransduction can be modulated by cytoskeleton, cell surface receptors such as integrins and proteoglycans, the chemical and physical properties of extracellular matrix (ECM) and cell-cell adhesions. The shear stress applied on the luminal surface of ECs can be sensed by cell membrane and associated receptor and transmitted throughout the cell to cell-ECM adhesions and cell-cell adhesions. As a result, shear stress induces directional migration of ECs by promoting lamellipodial protrusion and the formation of focal adhesions (FAs) at the front in the flow direction and the disassembly of FAs at the rear. Persistent EC migration in the flow direction can be driven by polarized activation of signaling molecules and the positive feedback loops constituted by Rho GTPases, cytoskeleton, and FAs at the leading edge. Furthermore, shear stress-induced EC migration can overcome the haptotaxis of ECs. Given the hemodynamic environment of the vascular system, mechanotransduction during EC migration has a significant impact on vascular development, angiogenesis, and vascular wound healing.     

Olfactory cell derivation and migration

This special issue of the Journal of Molecular Histology is devoted to the unique phenomena of migration and adult neurogenesis observed in the olfactory system. Neural progenitors migrate from the olfactory placode and epithelium (OE) into the central nervous system (CNS) and from the forebrain ventricular region to the olfactory bulb (OB). Not unexpectedly, there are a number of controversies with regard to the mechanisms regulating these phenomena in both developing and adult animals. One especially controversial issue common to both the peripheral (OE) and central (OB) systems is the identity of the slowly dividing multipotent stem cell and the mechanisms regulating the lineage specification of these progenitors which eventually differentiate into neurons and glia. Nine contributions from leading laboratories address these and other issues with respect to progenitors and their integration into OE and OB circuitry in several species.