Collagen Ultrastructural Properties and Mechanosensing in the Mammalian Extracellular Matrix: A Theoretical Model From Epidermis to Bone Marrow

Extracellular matrix (ECM) components that transmit mechanical loads are ubiquitous in the mammalian body. Collagen, the primary structural component of most ECMs, is present throughout connective tissues (CTs) and forms a continuous fibrous scaffold that joins ECMs and extends from the epidermis to the bone marrow. Within each ECM, both fibrillar collagen and the interposed glycosaminoglycans (GAGs) and proteoglycans (PGs), which bind and retain water, dynamically adapt to functional requirements. In this review, we describe how type I and III fibrillar collagens, which are the predominant collagens found in the body, form fibrils of different sizes, structures, and orientations that allow them to resist and transmit tensile forces from the environment to the deeper bone marrow, and, in some tissues, to resist compressive loads. These collagen types are embedded within a viscous matrix of GAGs and PGs that mainly oppose compressive loads and further contribute to the mechanical and functional properties of the continuous collagen network. These factors are consistent with a theoretical model emphasizing a broad role for ECM systems in sensing, adapting, and transmitting external mechanical stimuli from the epidermis to the bone marrow, allowing these signals to act across the basement membrane, dermis, hypodermis, fascia superficialis, subcutaneous tissue, deep fascia, muscle sheaths, tendon, ligament, periosteum, bone, and endosteum.