The mechanics of fibrillar collagen extracellular matrix

Abstract

As a major component of the human body, the extracellular matrix (ECM) is a complex biopolymer network. The ECM not only hosts a plethora of biochemical interactions but also defines the physical microenvironment of cells. The physical properties of the ECM, such as its geometry and mechanics, are critical to physiological processes and diseases such as morphogenesis, wound healing, and cancer. This review provides a brief introduction to the recent progress in understanding the mechanics of ECM for researchers who are interested in learning about this relatively new subject of biophysics. This review covers the mechanics of a single ECM fiber (nanometer scale), the micromechanics of ECM (micrometer scale), and bulk rheology (greater than millimeter scale). Representative experimental measurements and basic theoretical models are introduced side by side. After discussing the physics of ECM mechanics, the review concludes by commenting on the role of ECM mechanics in healthy and tumorigenic tissues and the open questions that call for future studies at the interface of fundamental physics, engineering, and medical sciences.

Figure 1.. The hierarchical structure of collagen matrix

Entropic effects become increasingly important at greater spatial scales (left to right).

Figure 2.. The worm-like chain (WLC) model of polymers explains the entropic origin of the polymer elasticity

(A) A schematic of the WLC model of polymers. For simplicity, only planar configuration is considered, but the physics can be easily generalized into 3 dimensions, and the results differ only by numerical factors. (B) The force-extension relation obtained by numerically inverting Equation 4. Dashed line represents the linear approximation for small strains.

Figure 3.. The micromechanics of a collagen matrix is controlled by its microstructure

(A) The confocal reflection image showing the collagen fibers and the probe particle (arrow). Inset: a holographic image showing the same field of view. (B) The particle displacements when an optical trap is projected at θ = 0° (red), 90° (green), 180° (blue), and 270° (magenta). The optical trap is projected at the same focal plane of the particle, and 0.7 μm from the unperturbed particle center. The power of the optical trap switches on and off at a frequency of 1 Hz. (C) Confocal reflection images showing distinct collagen fiber networks self-assembled at 2 different temperatures, 37°C and 21°C. (D) Spatial distributions of micromechanical compliance in 2 collagen matrices formed at 37°C and 21°C, respectively. (E) Spatial distributions of micromechanical anisotropy in 2 collagen matrices formed at 37°C and 21°C, respectively. Scale bars in (C)–(E): 50 μm. Adapted from Jones et al. Copyright (2016) National Academy of Sciences.

Figure 4.. The bulk rheological properties of a typical collagen matrix

(A) The elastic modulus of a reconstituted collagen matrix. The matrix contains a collagen concentration of 1.5 mg/mL. (B) The complex modulus-storage modulus and loss modulus of a reconstituted collagen matrix measured at various frequencies. The matrix contains a collagen concentration of 1.5 mg/mL. Adapted from Kim et al. Copyright (2017) Springer Nature Limited.

Figure 5.. A schematic illustration of affine deformation of polymer networks

In the affine model, every polymer in the network experiences an average strain based on its orientation. Under shear, there will be an equal number of fibers being stretched (the red fiber, for instance) and compressed (the yellow fiber, for instance).

Figure 6.. An example of a lattice-based model predicts nonlinear elasticity of semiflexible polymer networks

Left: the schematics of the model network. Right: the theoretically predicted nonlinear elasticity of the model network.

Figure 7.. Simulations of the phantom model help reveal the nature of the nonlinear elasticity of collagen matrices

(A) The network configuration at a small shear strain of γ = 0:5%. The color represents the ratio of stretching and bending energy of each fiber. (B) The network configuration at a large strain of γ = 50%. (C) The contribution of bending and stretching energies to the total elastic energy at varying strains. In (A)–(C) the network has a coordination number of 〈z〉 = 3:4. Adapted from Kim et al. Copyright (2017) Springer Nature Limited.

Figure 8.. The strain relaxation kinetics of collagen matrices demonstrates plasticity

(A) The shear relaxation from various initial strains. (B) The plastic timescale increases with longer dwell time. (C) The residual strain increases with longer dwell time. Adapted from Kim et al. Copyright (2017) Springer Nature Limited.

Figure 9.. The negative feedback loop mediated by the ECM synthesizes, and degradation allows the tissue to restore homeostasis after injury

After tissue injury, the coordinated ECM synthesizes, and degradation heals the wound and restores the dynamical ECM homeostasis.

Figure 10.. The ECM may promote tumorigenesis through a number of pathways

Cancer cells can physically remodel the surrounding ECM, thereby creating a microenvironment promoting tumorigenesis and metastasis.