Development of a 3D Computational Cell Model for Understanding Membrane-Cytoskeleton Interaction

Active biomaterials have unique properties such as high biocompatibility, biodegradability, and the ability to consume biological energy sources. The cytoskeletal network in a cell is a representative active biomaterial. The network is consisting of cytoskeletal proteins, cytoskeleton crosslinkers, and motor proteins. Sliding motion of the cytoskeletal filament is generated by the motor protein and developed into the network contraction.<br/>The cell membrane is an interface between cell and its external environment. Cell motions are determined by the deformation of the cell membrane. The deformation of the cell membrane is induced by the contraction of the cytoskeletal network which is connected to the membrane. The interaction between the membrane and the cytoskeletal network is a key factor for understanding cell deformation. However, the complexity of cellular components makes it difficult to understand how the contraction of the cytoskeletal network is developed into cell deformation via the cell membrane.<br/>Computational modeling is an effective approach for building a simplified system of cell. Some studies reported that the crosslinking degree of cytoskeletal filaments in the network defined by the ratio of cytoskeletal protein to cytoskeleton crosslinkers is closely related to the contractility of cytoskeletal network. However, it remains unclear the exact process by which the membrane transmits the mechanical force from the contractile cytoskeletal network to induce cell contraction.<br/>In our study, we developed a 3D computation model of cell membrane-cytoskeleton interaction including cytoskeletal filaments, motor proteins, cytoskeleton crosslinkers, the cell membrane, and membrane-cytoskeleton linkers on the membrane. We assessed membrane rigidity through thermal fluctuation analysis and replicated the rigidity of cell membrane by adjusting the stiffness of fiber linkers consisting of the membrane. Cytoskeletal filaments were attached to the membrane via membrane-cytoskeleton linker. We explored how the contraction shape changes based on the membrane properties, cytoskeleton crosslinking degree, and membrane-cytoskeleton linker concentration.<br/>Our simplified 3D cell model provides an insight for understanding the interactions between active components and membrane generating cell deformation. Our model and approaches for membrane modeling can help elucidate the mechanisms of cell functions such as division and migration in biological tissues. Additionally, we propose a design concept for a 3D cell-sized, stimuli-responsive smart material.