Active self-organization and maturation of mechanosensitive bio-molecular condensates
ORAL
Abstract
Mechanosensitive biomolecular condensates such as focal adhesions and adherens junctions form through liquid-liquid phase separation and are continuously reshaped by mechanical loads and biochemical turnover. We present a mechanochemical framework based on a Cahn-Hilliard reaction diffusion model with force-dependent binding and unbinding kinetics. Linear and eigenvalue analyses reveal that a uniform system can destabilize under a parameter regime influenced by mechanical forces, resulting in spatial patterns of focal adhesion, such as condensates with a definite length scale, which can subsequently oscillate in time to produce recurring load-fail cycles. Nonlinear simulations show that reactions suppress Ostwald ripening, producing microphase separation with a force and reaction-tunable wavelength. The stiffness of the condensate environment modulates the frequency and amplitude of load fail cycles, revealing that intermediate stiffness is required for sustained oscillations. Simulations performed in domains representing micropatterned cells, including triangular, square, and elliptical geometries, demonstrate that condensates preferentially nucleate in regions of high curvature, with spatial organization influenced by cell shape and boundary mechanics. This framework provides testable predictions for oscillation frequencies, characteristic length scales, and spatial organization as functions of mechanical and biochemical reactions and the geometry of the domain, linking subcellular mechanics to cell-scale mechanical behavior.
–
Presenters
-
Waleed Ahmad Mirza
- European Molecular Biology Laboratory in Heidelberg (EMBL)