Research Summary

Mechanisms and functional consequences of compositional regulation at the local and global scale in membranes of living cells

My research group’s goal is to uncover physico-chemical rules and principles that govern local regulated organization of the cell membrane. This will help us understand how the cell constructs functional signalling complexes and responsive endocytic platforms.

To study phenomena at the cellular scale, we utilize principles from the physical sciences to frame questions about movement of molecules and organelles inside cells. We have also developed numerous microscopy tools to study organization of cellular components, from the nanometer scale in specialized domains in cell membranes to the micron scale prevalent in mapping endocytic pathways. We study sorting properties and endocytic pathways of a variety of molecules, including membrane proteins, lipids and lipid-tethered proteins in vivo. Our studies provide a compelling picture of the cell membrane as an active composite of the lipid bilayer and a dynamic cortical actin layer beneath. The model suggests that dynamic actin filaments help in controlling the local composition of membranes and in shaping endocytic trafficking.

The trajectory of our work has led us to explore the fine structure of the plasma membrane, providing for the first time, an in vivo picture of lipidic assemblies. This has provided a new understanding of how membrane rafts may be created, insights into the role of specialized endocytic mechanisms for the establishment of developmental gradients and the regulation of membrane tension.

 

Figure 1. Nanoclusters are built by contractile actin platforms, resembling asters, and transbilayer coupling and mechanisms for nanocluster formation of outer leaflet lipid-anchored proteins.

 

Figure : 2 There are three scales at which the composition of the cell membrane may controlled, i) the local or mesoscopic scale, typically around the membrane receptor or at a nanometer-scale, ii) the micron scale; and iii) the scale of the entire plasma membrane. Here, I plan to address how the cell effects control at each scale.

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