Differential Actin Binding Affinity Leads to Protein Sorting in a Reconstituted Active Composite Layer

Abstract

Various functional cell surface proteins bind to cortical actin and undergo transient clustering driven by actomyosin flows. Examples include the GPI-anchored proteins, Ras-signalling proteins, T-cell receptors and many glycoproteins such as CD44. Given the density and diversity of protein and lipid species in the plasma membrane, the question arises how the local accumulation of specific molecules is achieved in a timely manner. Here we explore the possibility that the combination of differential binding of surface molecules to actin and the non-equilibrium acto-myosin dynamics leads to molecular patterning and cluster formation of membrane proteins. Using reconstituted acto-myosin networks tethered to supported lipid bilayers, as well as theoretical simulations, we provide evidence for this proposed active sorting mechanism. We show that differential affinity for actin templates a variety of patterns of membrane tethered proteins, including complete segregation, bull's eye and mixed pattern. Our results suggest that this mechanism could help in understanding the spatio-temporal organization and regulation of various processes at the cell surface.