Emergence of form from function—Mechanical engineering approaches to probe the role of stem cell mechanoadaptation in sealing cell fate

Abstract

ABSTRACT. Stem cell "mechanomics" refers to the effect of mechanical cues on stem cell and matrix biology, where cell shape and fate are intrinsic manifestations of form and function. Before specialization, the stem cell itself serves as a sensor and actuator; its structure emerges from its local mechanical milieu as the cell adapts over time. Coupling of novel spatiotemporal imaging and computational methods allows for linking of the energy of adaptation to the structure, biology and mechanical function of the cell. Cutting edge imaging methods enable probing of mechanisms by which stem cells' emergent anisotropic architecture and fate commitment occurs. A novel cell-scale model provides a mechanistic framework to describe stem cell growth and remodeling through mechanical feedback; making use of a generalized virtual power principle, the model accounts for the rate of doing work or the rate of using energy to effect the work. This coupled approach provides a basis to elucidate mechanisms underlying the stem cell's innate capacity to adapt to mechanical stimuli as well as the role of mechanoadaptation in lineage commitment. An understanding of stem cell mechanoadaptation is key to deciphering lineage commitment, during prenatal development, postnatal wound healing, and engineering of tissues.

Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals

“…Coupling these technologies has revealed great insights into dynamic bone (re)modelling via comparisons between mechanical loading and structural changes in bone tissue (6, 9–11). As these imaging and computational modelling methods have matured, they have become accurate enough to inform techniques such as laser capture microdissection to investigate individual cells within the bone tissue, and to perform “mechanomic” analysis, reconciling genetic responses to mechanical stimuli (12, 13) of the acquired cells (14, 15). The extraction of small populations of cells (16) and the assessment of their molecular and genetic profiles (17) has been combined with computational predictions of mechanical loads within the local in vivo environment (L iv E) of these cells (17), advancing our understanding of how organ-scale loads influence individual cells and the resultant (re)modelling behaviour.…”

Scale-up of nature’s tissue weaving algorithms to engineer advanced functional materials

“…Natural materials such as animal and plant tissues exhibit remarkable stimuli responsive (smart) and adaptive properties that emerge macroscopically from the anisotropic multicellular assembly and directional secretion of nanoscopic extracellular matrix proteins: in essence, the cells themselves “spin and weave” the tissue in situ 1. While top-down engineering approaches have elucidated multiscale structure-function relationships in a variety of tissue types, bottom-up approaches enable the engineering of so-called “emergent properties”23.…”

“…One bottom-up approach to engineer this “emergence” is to emulate nature’s paradigm for synthesizing smart tissue fabrics, through technological platforms that enable the weaving of multiscale, anisotropic biomaterials by cells themselves1. While perfect control of such stem cell behavior presents currently insurmountable hurdles, some inroads have been made in guiding the assembly of higher order tissue architectures using bottom-up approaches3.…”

“…The periosteum serves as an interface between bone and muscles and thus as a gatekeeper for transfer of molecular and physical (stresses, strains) information between the two tissue compartments1314. Like Velcro, collagen containing Sharpey’s fibers anchor periosteum to bone, serving as a link between the external musculature and the internal skeleton115. Due to the distribution and intrinsic strength of Sharpey’s fibers, periosteum remains attached to bone even after significant trauma15.…”

“…Remarkably this smart soft tissue increases the failure strength (load at failure) and stability (maintenance of structure, alignment) during fractures of hard bone1516. Furthermore, periosteum exhibits direction dependent (muscle <=> bone) and flow rate dependent permeability as well as mechanical properties, making it more permeable and stronger under impact loads12151617.…”