Li Haiyue, Xu Bin, Zhou Enhua H, Sunyer Raimon, Zhang Yanhang
Ophthalmology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Institute for Bioengineering of Catalonia, Baldiri-Reixac 15-21, 08028, Barcelona, Spain.
ACS Biomater Sci Eng. 2017 Nov 13;3(11):2815-2824. doi: 10.1021/acsbiomaterials.6b00634. Epub 2017 Jan 27.
The underlying mechanisms by which extracellular matrix (ECM) mechanics influences cell and tissue function remain to be elucidated because the events associated with this process span size scales from tissue to molecular level. Furthermore, ECM has an extremely complex hierarchical 3D structure and the load distribution is highly dependent on the architecture and mechanical properties of ECM. In the present study, the macro- and microscale mechanical properties of collagen gel were studied. Dynamic rheological testing was performed to study the macroscale mechanical properties of collagen gel. The microscale mechanical properties of collagen gel were measured using optical magnetic twisting cytometry (OMTC). Ferromagnetic beads embedded in the matrix were used as mechanical probes. Our study on the multiscale mechanical properties of collage matrix suggests several interesting differences between macro and microscale mechanical properties originated from the scales of measurements. At the macroscopic scale, storage and loss modulus increase with collagen concentrations. Nonaffine collagen fibril structural network deformation plays an important role in determining the macroscopic mechanical properties of the collagen matrix. At the microscopic scale, however, the local mechanical properties are less sensitive to changes in collagen concentration because of the more immediate/direct deformation of collagen fibrils in the OMTC measurements through forces exerted by locally attached ferromagnetic beads. The loss modulus is more affected by the local interstitial fluid environment, leading to a rather dramatic increase in viscosity with frequency, especially at higher frequencies (>10 Hz). A finite element model was developed to study the geometric factors in the OMTC measurements when the collagen matrix was considered to be hyperelastic. Our results show that the geometric factors are dependent on collagen concentration, or the stiffness of matrix, when nonlinear material properties of the matrix are considered, and thus interpretation of the apparent modulus from OMTC measurements should be conducted carefully.
细胞外基质（ECM）力学影响细胞和组织功能的潜在机制仍有待阐明，因为与该过程相关的事件跨越了从组织到分子水平的大小尺度。此外，ECM具有极其复杂的分层三维结构，且载荷分布高度依赖于ECM的结构和力学性能。在本研究中，对胶原凝胶的宏观和微观力学性能进行了研究。通过动态流变学测试来研究胶原凝胶的宏观力学性能。使用光磁扭转细胞术（OMTC）测量胶原凝胶的微观力学性能。嵌入基质中的铁磁珠用作力学探针。我们对胶原基质多尺度力学性能的研究表明，宏观和微观力学性能之间存在一些有趣的差异，这些差异源于测量尺度。在宏观尺度上，储能模量和损耗模量随胶原浓度增加。非仿射胶原纤维结构网络变形在决定胶原基质的宏观力学性能中起重要作用。然而，在微观尺度上，由于在OMTC测量中胶原纤维通过局部附着的铁磁珠施加的力产生更直接的变形，局部力学性能对胶原浓度变化不太敏感。损耗模量受局部间质液环境影响更大，导致粘度随频率显著增加，尤其是在较高频率（>10Hz）时。当将胶原基质视为超弹性时，开发了一个有限元模型来研究OMTC测量中的几何因素。我们的结果表明，当考虑基质的非线性材料特性时，几何因素取决于胶原浓度或基质的刚度，因此应谨慎解释来自OMTC测量的表观模量。
