Mostly Biomathematics Lunchtime Seminar

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Reconstructing Dynamics of the Cell's Leading Edge from Observational Data

Speaker: Wenzheng Shi, Courant Institute, New York University

Location: Warren Weaver Hall 1314

Date: Tuesday, October 21, 2025, 12:45 p.m.

Synopsis:

Mesenchymal cell migration starts with protrusion of the cell leading edge, which is enabled by branching growth of actin network pushing against the plasma membrane. Two crucial molecular players in this process are actin filaments and Arp2/3 protein complex, the branching agent. Traditionally, actin protrusion models are intuited from limited experimental data in the form of continuous dynamical systems or discrete agent-based models. Recent multiplex microscopy imaging data promise to drastically change this limitation by providing measurements of naturally fluctuating densities of key proteins at the leading edge of unperturbed cells. Here, we report the first attempt of reconstructing the protrusion model from such data. We analyze the fluctuations of actin and Arp2/3 densities and cell edge velocity using phase space and regression analyses to reconstruct linear perturbations and noise terms of actin-Arp2/3-velocity coupled dynamics. We then build deterministic PDE model and stochastic agent-based model of these dynamics using heuristic arguments based on previous knowledge of this system and parsimony. The resulting model confirms previously obtained insights about the cell protrusion, posits several nontrivial mechanochemical relations at the cell leading edge, and proposes an explanation for the high measured level of molecular noise.