4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Graphical abstract

          Highlights

          • Summarize the soft materials promoting intracellular force and the “hard” downstream phenotypes.

          • Understand the soft materials dynamically adapting to the mechanical changes at the cell-environment interface.

          • Summarize the general mechanosensing mechanism of the cells on/in adaptable soft materials.

          Related collections

          Most cited references71

          • Record: found
          • Abstract: found
          • Article: not found

          Effects of extracellular matrix viscoelasticity on cellular behaviour

          Significant research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, impacts fundamental cell processes including spreading, growth, proliferation, migration, differentiation, and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins have become widely-used tools for assessing the role of stiffness, and results from these experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo . However, tissues and ECMs are not linearly elastic materials – they in fact exhibit far more complex mechanical behaviors, including viscoelasticity, or a time-dependent response to loading or deformation, as well as mechanical plasticity and nonlinear elasticity. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and importantly can promote behaviors not observed with elastic hydrogels in both 2D and 3D culture microenvironments. These important findings have provided new insights into cell-matrix interactions and have given context as to how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results indicate new design guidelines for the next generation of biomaterials that better match tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Hydrogels with tunable stress relaxation regulate stem cell fate and activity

            Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel’s initial elastic modulus, cell-adhesion-ligand density and degradation. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The extracellular matrix: not just pretty fibrils.

              The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.
                Bookmark

                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                27 August 2021
                April 2022
                27 August 2021
                : 10
                : 397-404
                Affiliations
                [a ]College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, Chengdu, 610065, China
                [b ]Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China
                [c ]Joint Appointment with School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China
                [d ]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China
                Author notes
                []Corresponding author. College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, Chengdu, 610065, China. wei@ 123456scu.edu.cn
                [∗∗ ]Corresponding author. Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China. zqchu@ 123456eee.hku.hk
                [1]

                There authors contribute equally to this work.

                Article
                S2452-199X(21)00402-3
                10.1016/j.bioactmat.2021.08.026
                8636665
                34901555
                28cece80-063d-4b4c-bc27-83cc0735e715
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 6 July 2021
                : 15 August 2021
                : 23 August 2021
                Categories
                Article

                cell,mechanotransduction,intracellular force,biomaterials,soft materials

                Comments

                Comment on this article