Effect of matrix heterogeneity on cell mechanosensing

Abstract

Cells sense mechanical signals within the extracellular matrix, the most familiar being stiffness, but matrix stiffness cannot be simply described by a single value. Randomness in matrix structure causes stiffness...

Magnetic microrheometry of tumor-relevant stiffness levels and probabilistic quantification of viscoelasticity differences inside 3D cell culture matrices

“…The measured viscoelastic properties can be assigned to specific points within the matrix, whereas-in an ideal homogeneous material-such values are constant at each point/location. The most of the used 3D culture matrices are known to exhibit heterogeneous or spatially varying viscoelastic properties [25,[28][29][30].…”

“…Further, recent research shows that the matrix viscoelasticity not only involves sample-to-sample variation, but each of the matrix samples may exhibit internal variation that is referred to as heterogeneity in viscoelasticity [25]. Due to the heterogeneity, viscoelastic properties in multiple 3D-culture matrices vary spatially [25,[28][29][30][31]. Each cell senses the stiffness of its environment at the microscale [16,32] as well as other viscoelasticity-related properties [11], and responds to those mechanical stimuli.…”

Micromechanical remodeling of the extracellular matrix by invading tumors: anisotropy and heterogeneity

“…Therefore a cancer cell will directly modify and respond to the ECM micromechanics at the cellular scale, [22][23][24] and may not have the knowledge of their physical environment at scales hundreds of times larger. 25 The distinct mechanical properties of the ECM at cellular and tissue scales can be traced back to the ECM structure. Collagen ECM, for example, is a disordered assembly of fibrous scaffold with pore sizes ranging from sub-micrometer to a few micrometers.…”

“…Therefore a cancer cell will directly modify and respond to the ECM micromechanics at the cellular scale, 22–24 and may not have the knowledge of their physical environment at scales hundreds of times larger. 25…”

Microstructured click hydrogels for cell contact guidance in 3D

“…For example, the inclusion of short magnetic-responsive microelements in soft hydrogels generated sophisticated injectable biomaterials with the ability to direct neuronal cell growth and orientation [ 9 , 10 ]. Remarkably, even if presented to cells in a random fashion, the inclusion of stiffer microelements inside an hydrogel matrix provides a way to guide cellular organization via mechanosensing mechanisms [ 11 ]. Still, most strategies reported so far rely on the use of hybrid systems combining different components, which brings complexity to the approach and may hamper clinical translation [ 12 ].…”