Revealing Layer‐Specific Ultrastructure and Nanomechanics of Fibrillar Collagen in Human Aorta via Atomic Force Microscopy Testing: Implications on Tissue Mechanics at Macroscopic Scale

Abstract

Soft biological tissues are natural biomaterials with structures that have evolved to perform physiological functions, for example, conferring elasticity while preserving the mechanical integrity of arteries. Furthermore, the mechanical properties of the tissue extracellular matrix (ECM) significantly affect cell behavior and organ function. ECM mechanical properties are strongly affected by collagen ultrastructure, and perturbations in collagen networks can cause tissue mechanical failure. It is thus crucial to understand the ultrastructural mechanical properties of soft tissues. Herein, the ultrastructural and nanomechanical properties of arterial tissues are reported. Specifically, maps of aorta tissue stiffness in its three constitutive layers, namely tunica intima, media, and adventitia, are reported. Atomic force microscopy (AFM) with large and ultrasharp tips is used to explore tissue stiffness at two scales. Quasistatic tensile tests are further conducted to understand a potential correspondence between small‐scale mechanical properties obtained via AFM indentation and macroscopic behavior of the tissue at low and large strains. Furthermore, gradients in stiffness across the various layers as well as deformation rate effects are investigated. It is envisioned that the established methodology serves as a tool to investigate the effect of ECM remodeling associated with vascular diseases such as aneurysms and arterial stiffening linked to hypertension.

Effects of the Combined Application of Trimethylated Chitosan and Carbodiimide on the Biostability and Antibacterial Activity of Dentin Collagen Matrix

“…Fibrillar collagen is a strong and elastic biomaterial arranged in a highly organized hierarchy [ 35 , 36 ]. Type I collagen, the most prevalent of all collagen types, is a coiled helical trimeric molecule made up of repeating sequences of the amino acids Gly-XY, where X and Y are typically found as proline and hydroxyproline [ 16 ].…”

Determining Spatial Variability of Elastic Properties for Biological Samples Using AFM

“…Young’s modulus maps were created using the classic Hertzian approach (Equation (7)) and revealed that Young’s modulus varies between 0.1 KPa to 10 KPa depending on the body area and dermal layer [ 33 ]. Another application is the recording of the ultrastructural and nanomechanical properties of arterial tissues [ 34 ]. The tissue stiffness has been explored using the AFM indentation method.…”

“…AFM with large and ultrasharp tips was used to explore tissue stiffness at two scales. Spherical probes for experiments at the micro-scale (tip radius ~2 μm) and sharp probes for experiments at the nanoscale (tip radius ~2 nm) were used [ 34 ]. Hertzian mechanics has also been used for data processing regarding experiments in individual collagen fibrils or collagen fibrils under the influence of external factors [ 3 , 4 ].…”

3D AFM Nanomechanical Characterization of Biological Materials

“…The need for an accurate 3D mechanical characterization using various approaches is growing fast, as was shown in [ 18 ], and is considered to be a cutting-edge area of research since the aim is to solve the most important problem in the mechanical characterization of biological samples, which is the current inability to record the mechanical properties at a 3D scale. In other words, existing AFM methods using typical Young’s modulus maps [ 19 , 20 , 21 , 22 , 23 , 24 ] provide a 2D characterization (since they do not take into account the alterations in mechanical properties’ in the 3rd dimension, i.e., as the indentation depth increases, and their results are user dependent).…”