Department of Molecular Biology & Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
Department of Molecular Biology & Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
Biophys J. 2022 Feb 15;121(4):515-524. doi: 10.1016/j.bpj.2022.01.013. Epub 2022 Jan 19.
Changes in biomechanical properties have profound impacts on human health. C. elegans might serve as a model for studying the molecular genetics of mammalian tissue decline. Previously, we found that collagens are required for insulin signaling mutants' long lifespan and that overexpression of specific collagens extends wild-type lifespan. However, whether these effects on lifespan are due to mechanical changes during aging has not yet been established. Here, we have developed two novel methods to study the cuticle: we measure mechanical properties of live animals using osmotic shock, and we directly perform the tensile test on isolated cuticles using microfluidic technology. Using these tools, we find that the cuticle, not the muscle, is responsible for changes in the "stretchiness" of C. elegans, and that cuticle stiffness is highly nonlinear and anisotropic. We also found that collagen mutations alter the integrity of the cuticle by significantly changing the elasticity. In addition, aging stiffens the cuticle under mechanical loads beyond the cuticle's healthy stretched state. Measurements of elasticity showed that long-lived daf-2 mutants were considerably better at preventing progressive mechanical changes with age. These tests of C. elegans biophysical properties suggest that the cuticle is responsible for their resilience.
生物力学特性的变化对人类健康有深远的影响。秀丽隐杆线虫可能成为研究哺乳动物组织衰退的分子遗传学模型。先前,我们发现胶原蛋白是胰岛素信号突变体长寿所必需的,并且特定胶原蛋白的过表达可以延长野生型寿命。然而,这些对寿命的影响是否是由于衰老过程中的机械变化尚不清楚。在这里,我们开发了两种研究表皮的新方法:我们使用渗透压休克测量活体动物的力学特性,并用微流控技术直接对分离的表皮进行拉伸测试。使用这些工具,我们发现是表皮,而不是肌肉,导致秀丽隐杆线虫的“弹性”发生变化,并且表皮的刚性具有高度的非线性和各向异性。我们还发现胶原突变通过显著改变弹性来破坏表皮的完整性。此外,在机械负载下,衰老使表皮变硬,超出了表皮健康拉伸状态。弹性测量表明,长寿命的 daf-2 突变体在防止随着年龄增长而发生的渐进性机械变化方面要好得多。这些秀丽隐杆线虫生物物理特性的测试表明,表皮是其弹性的原因。