Executive Summary : | Cell signaling is a crucial biophysical process that allows cells to communicate with their surroundings, leading to various diseases such as cancers. Understanding this process is crucial in information processing, as cells encode, decode, and process signals through unexplored biophysical processes. The plasma membrane (PM), which separates the cell from the outside, is crucial for encoding and decoding signals. Recent experimental data has shown that lipids on the PM rapidly rearrange in response to signals, resembling dynamic heterogeneity in dynamic materials. The authors propose investigating the origin of nanoscale dynamic heterogeneity on the cell membrane. They hypothesize that the origin of membrane heterogeneity is its interaction with the cortical actin cytoskeleton (ACS), which displays dynamic heterogeneity. This hypothesis will be tested through theory and multiscale simulations, identifying and investigating its consequences, and providing falsifiable predictions. Two related approaches will be used to achieve these goals. The first approach will mathematically analyze spatiotemporal maps of diffusivities to develop an intuition about the underlying distributions of lipids on the cell membrane. The developed intuitions will be consolidated through multiscale simulations of an ACS-membrane composite, solving a dynamic density functional theory model parameterized by explicit atomistic simulations. The proposed projects will provide a deep understanding of how the crosstalk between cell mechanics and cell membrane dynamics allows cells to respond to signals. These projects will enable us to probe the nonequilibrium response of the cell membrane during cell signaling, ultimately helping solve the information processing puzzle and understanding the biology of cell signaling. |