Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signaling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.
Cells interact with their environment by forming complex structures involving a multitude of proteins within assemblies in the plasma membrane. Despite the omnipresence of these assemblies, a number of questions about the correlations between the organisation of domains and the biomechanical properties of the involved proteins, namely their length, flexibility and affinity, as well as about the coupling to the elastic, fluctuating membrane, remain open. Here we address these issues by developing an effective Kinetic Monte Carlo simulation to model membrane adhesion. We apply this model to a typical experiment in which a cell binds to a functionalized solid supported bilayer and use two ligand-receptor pairs to study these couplings. We find that differences in affinity and length of proteins forming adhesive contacts result in several characteristic features in the calculated phase diagrams. One such feature is mixed states occurring even with proteins with length differences of 10 nm. Another feature are stable nanodomains with segregated proteins appearing on time scales of cell experiments, and for biologically relevant parameters. Furthermore, we show that macroscopic ring-like patterns can spontaneously form as a consequence of emergent protein fluxes. The capacity to form domains is captured by an order parameter that is founded on the virial coefficients for the membrane mediated interactions between bonds, which allow us to collapse all the data. These findings show that taking into account the role of the membrane allows us to recover a number of experimentally observed patterns. This is an important perspective in the context of explicit biological systems, which can now be studied in significant detail.
We study a model of a lipid bilayer membrane described by two order parameters: the chemical composition described using the Gaussian model and the spatial configuration described with the elastic deformation model of a membrane with a finite thickness, or equivalently, for an adherent membrane. We assume and explain on physical grounds the linear coupling between the two order parameters. Using the exact solution, we calculate the correlation functions and order parameters profiles. We also study the domains that form around inclusions on the membrane. We propose and compare six distinct ways to quantify the size of such domains. Despite of its simplicity, the model has many interesting features like Fisher-Widom line or two distinct critical regions.
Specific lipid environments are necessary for the establishment of protein signalling platforms in membranes, yet their origin has been highly debated. We present a continuum, exactly solvable model of protein induced local demixing of lipid membranes. The coupling between a local composition and a local thickness of the membrane induces lipid domains around inclusions with hydrophobic mismatch, even for temperatures above the miscibility critical point of the membrane. The model qualitatively explains the experimentally observed formation of lipid domains induced by anchoring of reconstituted actin in flat supported lipid bilayers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.