A Dynamic Biochemomechanical Model of Geometry-Confined Cell Spreading

BPJ_112_11.c1.inddCell spreading is involved in many physiological and pathological processes. In confluent multicellular systems, the dynamic evolution of an individual cell is influenced by its neighbors. It has been recognized that microsystems (e.g., microchambers) with defined geometry can affect the spatiotemporal dynamics of cells. However, it remains unclear how cells sense and respond to geometric confinement at the subcellular level. We answer this question by establishing a dynamic biochemomechanical model of geometry-confined cell spreading. This model reveals that the positioning of the cell-division plane is strongly affected by its boundary confinement.

The cover image for the June 6 issue of the Biophysical Journal illustrates the dynamic configurational evolution of a cell (blue) spreading in an L-shaped microchamber (silver). Its nucleus and microtubules are represented by the green sphere and emanated lines, respectively. The cell flattens and forms lamellipodia on the substrate but cannot step over the side walls of the chamber. In the initial spreading stage, the cell takes a round shape and spreads isotropically on the substrate before contacting the chamber boundary. The nucleus is positioned at its mass center (remote). Once the cell membrane contacts the chamber boundary, it may slide along or be fixed on the latter, depending on the force equilibrium condition (middle). For a cell undergoing anisotropic spreading, the length-dependent microtubule forces can drive the nucleus to move. Finally, the spreading cell reaches a steady-state configuration, which dictates the nuclear deformation and the cell-division plane (near).

The cover image was inspired by the cell spreading dynamics model which integrates biological, chemical, and mechanical mechanisms based on experimental observations. More details of the model can be found in our Biophysical Journal paper. This interdisciplinary work helps understand how microenvironments affect the spreading dynamics and division of cells. The findings also have potential applications in regulating cell division and designing cell-based sensors.

– Zi-Long Zhao, Zong-Yuan Liu, Jing Du, Guang-Kui Xu, Xi-Qiao Feng

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