Department of Applied Chemistry and Chemical Engineering, Faculty of Science, University of Chittagong, Bangladesh.
Biomater Sci. 2020 Dec 15;8(24):7033-7081. doi: 10.1039/d0bm01255f.
In mammals, mechanics at multiple stages-nucleus to cell to ECM-underlie multiple physiological and pathological functions from its development to reproduction to death. Under this inspiration, substantial research has established the role of multiple aspects of mechanics in regulating fundamental cellular processes, including spreading, migration, growth, proliferation, and differentiation. However, our understanding of how these mechanical mechanisms are orchestrated or tuned at different stages to maintain or restore the healthy environment at the tissue or organ level remains largely a mystery. Over the past few decades, research in the mechanical manipulation of the surrounding environment-known as substrate or matrix or scaffold on which, or within which, cells are seeded-has been exceptionally enriched in the field of tissue engineering and regenerative medicine. To do so, traditional tissue engineering aims at recapitulating key mechanical milestones of native ECM into a substrate for guiding the cell fate and functions towards specific tissue regeneration. Despite tremendous progress, a big puzzle that remains is how the cells compute a host of mechanical cues, such as stiffness (elasticity), viscoelasticity, plasticity, non-linear elasticity, anisotropy, mechanical forces, and mechanical memory, into many biological functions in a cooperative, controlled, and safe manner. High throughput understanding of key cellular decisions as well as associated mechanosensitive downstream signaling pathway(s) for executing these decisions in response to mechanical cues, solo or combined, is essential to address this issue. While many reports have been made towards the progress and understanding of mechanical cues-particularly, substrate bulk stiffness and viscoelasticity-in regulating the cellular responses, a complete picture of mechanical cues is lacking. This review highlights a comprehensive view on the mechanical cues that are linked to modulate many cellular functions and consequent tissue functionality. For a very basic understanding, a brief discussion of the key mechanical players of ECM and the principle of mechanotransduction process is outlined. In addition, this review gathers together the most important data on the stiffness of various cells and ECM components as well as various tissues/organs and proposes an associated link from the mechanical perspective that is not yet reported. Finally, beyond addressing the challenges involved in tuning the interplaying mechanical cues in an independent manner, emerging advances in designing biomaterials for tissue engineering are also explored.
在哺乳动物中，从发育到繁殖再到死亡的过程中，多个阶段的力学——从细胞核到细胞到细胞外基质——为多种生理和病理功能提供了基础。受此启发，大量研究已经确定了力学的多个方面在调节基本细胞过程中的作用，包括扩散、迁移、生长、增殖和分化。然而，我们对于这些力学机制如何在不同阶段进行协调或调整以维持或恢复组织或器官水平的健康环境仍然知之甚少。在过去的几十年中，对周围环境力学的操控研究——即在细胞接种的基质或支架上或内部进行操作——在组织工程和再生医学领域得到了极大的丰富。为此，传统的组织工程旨在将天然细胞外基质的关键力学里程碑重现在基质中，以指导细胞命运和功能向特定的组织再生方向发展。尽管取得了巨大的进展，但仍有一个大难题，即细胞如何以协作、受控和安全的方式将大量力学线索（如刚度（弹性）、粘弹性、塑性、非线性弹性、各向异性、力学力和力学记忆）转化为许多生物学功能。高通量理解关键细胞决策以及相关的机械敏感性下游信号通路（在单独或组合的情况下）对于执行这些决策以响应机械线索至关重要。虽然已经有许多报告针对机械线索（特别是基质的整体刚度和粘弹性）调节细胞反应的进展和理解进行了报道，但机械线索的全貌仍然缺失。本综述强调了与调节许多细胞功能和随后的组织功能相关的机械线索的综合观点。为了有一个基本的了解，简要讨论了细胞外基质的关键力学成分和力学转导过程的原理。此外，本综述还汇集了关于各种细胞和细胞外基质成分以及各种组织/器官的刚度的最重要数据，并从机械角度提出了尚未报道的相关联系。最后，除了解决独立调节相互作用的力学线索所涉及的挑战外，还探讨了用于组织工程的生物材料设计的新兴进展。
