Soft overcomes the hard: Flexible materials adapt to cell adhesion to promote cell mechanotransduction

Abstract

Cell behaviors and functions show distinct contrast in different mechanical microenvironment. Numerous materials with varied rigidity have been developed to mimic the interactions between cells and their surroundings. However, the conventional static materials cannot fully capture the dynamic alterations at the bio-interface, especially for the molecular motion and the local mechanical changes in nanoscale. As an alternative, flexible materials have great potential to sense and adapt to mechanical changes in such complex microenvironment. The flexible materials could promote the cellular mechanosensing by dynamically adjusting their local mechanics, topography and ligand presentation to adapt to intracellular force generation. This process enables the cells to exhibit comparable or even higher level of mechanotransduction and the downstream ‘hard’ phenotypes compared to the conventional stiff or rigid ones. Here, we highlight the relevant studies regarding the development of such adaptive materials to mediate cell behaviors across the rigidity limitation on soft substrates. The concept of ‘soft overcomes the hard’ will guide the future development and application of biological materials.

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

“…5 C, and D, the cell viability of the hydrogel IV group increased compared with that of the control group in 72 h, probably due to the hydrogel IV composed of chitosan and gelatin simulated the extracellular matrix (ECM) [ [40] , [41] , [42] ]. The cell viability of fibroblasts cultured with the hydrogel Ⅳ for 72 h in the high levels of glucose and MMP-9 increased by 36.54 ± 7.38% compared with that of the glucose + MMP-9 group, may be attributed to the synergistic effect: insulin was released from the hydrogel Ⅳ through response to the environment, and insulin promotes cell proliferation [ 43 ]; the hydrogel IV promoted cell proliferation by being degraded in the high levels of glucose and MMP-9 [ 42 ]. Improving migration has also been shown to promote wound healing [ 36 ], and insulin stimulates the migration of fibroblasts [ 44 ].…”

“…The results of the scratch assay and the wound closure rate are shown in Fig. 5 E and F. Compared with the control group, the cell mobility of the hydrogel Ⅳ group increased by 30.83 ± 6.19% within 24 h, which may be attributed to the fact that the hydrogel Ⅳ simulated the ECM to promote cell adhesion [ 42 ]. At high glucose concentrations (***P < 0.001), the increased migration ability of fibroblasts incubated with hydrogel IV within 24 h may be due to the fact that the hydrogel Ⅳ simulated the ECM while releasing insulin [ 44 ].…”

“…Celecoxib had no significant effect on the migration of fibroblasts for 24 h, and the small increase of cell mobility in the MMP-9 + hydrogel IV group within 24 h might be added the hydrogel Ⅳ. The increased migration of cells in the MMP-9 + Glucose + Hydrogel Ⅳ group in 24 h was attributed to the synergistic effect of the above reasons, and the hydrogel Ⅳ degraded faster in the high concentration of glucose and MMP-9, which also promoted fibroblasts adhesion and migration [ 42 ]. Importantly, compared with the glucose + insulin group, the glucose + hydrogel IV group promoted the migration of fibroblasts in the high concentration of glucose, which might be attributed to the use of hydrogel IV sustained-release insulin, which increased the utilization of insulin which with a short half-life [ 45 ].…”

Influences of viscosity on the osteogenic and adipogenic differentiation of mesenchymal stem cells with controlled morphology

“…10–12 A variety of surfaces and scaffolds with different stiffnesses have been prepared for investigating the stiffness-dependent differentiation of stem cells. 13–20 A soft matrix is beneficial for the differentiation of stem cells into the soft tissue cell lineage, and vice versa .…”

All-Optical Modulation of Single Defects in Nanodiamonds: Revealing Rotational and Translational Motions in Cell Traction Force Fields

“…The mechanical properties (e.g., stiffness and viscosity) of both natural and synthetic extracellular matrices significantly influence cell phenotype and functions. − Conversely, cells can also exert traction forces to their 3D surroundings. These tight interactions enable cells to rearrange their internal structures and adhesion molecules to adapt to the changing microenvironments, consequently enhancing their biological functions . Therefore, acquiring precise knowledge of the interplay between cells and their surroundings is critical for our understanding of mechanosensing and mechanotransduction.…”