Matrix elasticity, cytoskeletal forces and physics of the nucleus: how deeply do cells ‘feel’ outside and in?

Abstract

SummaryCellular organization within a multicellular organism requires that a cell assess its relative location, taking in multiple cues from its microenvironment. Given that the extracellular matrix (ECM) consists of the most abundant proteins in animals and contributes both structure and elasticity to tissues, ECM probably provides key physical cues to cells. In vivo, in the vicinity of many tissue cell types, fibrous characteristics of the ECM are less discernible than the measurably distinct elasticity that characterizes different tissue microenvironments. As a cell engages matrix and actively probes, it senses the local elastic resistance of the ECM and nearby cells via their deformation, and -similar to the proverbial princess who feels a pea placed many mattresses below -the cell seems to possess feedback and recognition mechanisms that establish how far it can feel. Recent experimental findings and computational modeling of cell and matrix mechanics lend insight into the subcellular range of sensitivity. Continuity of deformation from the matrix into the cell and further into the cytoskeleton-caged and -linked nucleus also supports the existence of mechanisms that direct processes such as gene expression in the differentiation of stem cells. Ultimately, cells feel the difference between stiff or soft and thick or thin surroundings, regardless of whether or not they are of royal descent.

Numerical modeling of cell differentiation and proliferation in force-induced substrates via encapsulated magnetic nanoparticles

“…The main objective here is to define a velocity-dependent opposing force associated with the viscous character of the substrate. Referring to Stokes' drag regime, the drag force acting on a spherical cell can be presented as [48,71] F drag = 6πrηv (8) where r and v are cell radius and velocity, respectively, while η is medium viscosity. Cells send out local protrusions to probe their environment by exerting a random protrusion force.…”

“…Here, it is assumed that there are magnetic nanoparticles encapsulated within a rigid sphere located in the middle of the substrate. Initially, the substrate stiffness is set to lower bounds of neurogenic (0.1-1 kPa), chondrogenic (20-25 kPa) and osteogenic cells (30-45 kPa) tissue stiffness [8]. Then, cell-cultured hydrogel is induced by a force in the longitudinal direction to increase the substrate rigidity.…”

“…To avoid repeating MSC proliferation, the results are represented starting from the instant of MSC differentiation. First, it is con- sidered that the substrate stiffness is equal to the lower bound of osteogenic substrates (30 kPa) [8] without inducing any internal force within the substrate. In order to study the effect of forceinduced substrate, an internal force (5 µN) is applied in the middle of the substrate in the longitudinal direction which increases the substrate local stiffness around a rigid sphere.…”

“…Again, to avoid the demonstration of the MSC proliferation process, the results are presented starting from the moment of MSC differentiation. The substrate stiffness is set to be the lower bound of chondrogenic tissue stiffness (20 kPa) [8] and it is induced by a 3 µN force in the longitudinal direction. MSC located near the rigid sphere is gradually maturated.…”

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

“…Previous experimental studies have established the mechanical link between the cytoskeleton and the nucleus (Buxboim et al 2010), and, in particular, that the removal of nuclear lamins also leads to disruption of the cytoskeleton (Broers et al 2004). In the current study, the nucleus and the cytoplasm are simulated as two separate but continuous regions and it is important to note that no movement is permitted between the cytoplasm and the nucleus.…”