Adaption of mechano-chemical self-organization at cellular membranes to extracellular stressors

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The plasma membrane is subject to continuous deformations that vary in length and amplitude. In response to such transient membrane deformations, curvature-sensitive molecules are dynamically recruited to these sites. Relevant for this proposal, some of these proteins are capable to locally change actin polymerization rates, and in consequence the force exerted to the membrane. This, in turn, creates receptor-independent feedback loops. In recent work, we identified such a curvature-dependent module that mediates exploratory search pattern in adherent single cells (Begemann et al., Nature Physics). We showed that this self-organizing module, which relies on dynamic recruitment of curvature-sensitive signaling molecules to deforming membranes at the leading edge (LE), alters motion pattern in a variety of single-cell model systems including immune cells. However, the consequences of external stressors on signal processing, and hence on search pattern via this module, have remained elusive. In this project, we aim to investigate how such inputs affect signaling and cell motion. Specifically, we will answer (i) how temperature alters curvature-dependent cellular motion pattern, and (ii) how substrate stiffness affects curvature-dependent cellular motion pattern. To address these questions, we will take advantage of state-of-the-art cellular, biophysical and computational tools that we developed in the lab. Collectively, these studies will allow us to gain novel insights into the fundamental question how a self-organizing signaling system adapts signaling for motion pattern under varying external conditions.