Enriquez Martinez Marco A, Wang Zhao, Alvarez Yanina D, O'Neill Jade E, Ju Robert J, Turunen Petri, White Melanie D, Mata Jitendra, Gilbert Elliot P, Lauko Jan, Rowan Alan E, Stehbens Samantha J
Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.
Institute for Molecular Biosciences (IMB), The University of Queensland, Brisbane, QLD 4072, Australia.
Sci Adv. 2025 Jun 20;11(25):eadt3352. doi: 10.1126/sciadv.adt3352.
In living tissues, collagen networks rarely exist alone because they are embedded within other biological matrices. When combined, collagen networks rigidify via synergistic mechanical interactions and stiffen only with higher mechanical loads. However, how cells respond to the nonlinear elasticity of collagen in hybrid networks remains largely unknown. Here, we demonstrate that when collagen rigidifies by the interpenetration of a second polymer, the amount of force that initially stiffens the network (onset of stiffening, σ) increases and is sufficient to stimulate an increase in intracellular tension. We investigated this effect by precisely controlling the nonlinear elasticity of collagen with the synthetic semiflexible polymer, polyisocyanopeptides. We find that small increases in σ induce a biphasic response in cell-matrix interactions, influencing how cells migrate, proliferate, and generate contractile force. Our results suggest that cells adaptively respond to changes in the nonlinear mechanics of collagen, which may be a mechanistic behavior used during tissue homeostasis or when collagen rigidifies during pathological conditions.
在活组织中，胶原网络很少单独存在，因为它们嵌入在其他生物基质中。当结合在一起时，胶原网络通过协同机械相互作用而变硬，并且仅在承受更高机械负荷时才会变硬。然而，细胞如何响应混合网络中胶原的非线性弹性在很大程度上仍然未知。在这里，我们证明，当胶原通过第二种聚合物的相互渗透而变硬时，最初使网络变硬的力的大小（变硬起始点，σ）会增加，并且足以刺激细胞内张力的增加。我们通过用合成半柔性聚合物聚异氰肽精确控制胶原的非线性弹性来研究这种效应。我们发现σ的小幅增加会在细胞-基质相互作用中引发双相反应，影响细胞的迁移、增殖和产生收缩力的方式。我们的结果表明，细胞会对胶原非线性力学的变化做出适应性反应，这可能是组织稳态期间或病理状态下胶原变硬时所采用的一种机械行为。
