Determining the fundamental mechanisms underlying tissue formation and wound healing allows for bio-inspired approaches that leverage the best practices of biology, as decided upon by millions of years of evolution. To gain insight into how tissue is built, we have studied the interactions between two of the principal proteins found in connective tissues: collagen and fibronectin. We have confirmed a binding affinity in solution, which supports a reciprocal relationship whereby the assembly pathway of one catalyzes the other. The molecular synergy enables complex extracellular matrix formation with a range of mechanical properties.
The ability to fabricate anisotropic collagenous materials rapidly and reproducibly has remained elusive despite decades of research. Balancing the natural propensity of monomeric collagen (COL) to spontaneously polymerize in vitro with the mild processing conditions needed to maintain its native substructure upon polymerization introduces challenges that are not easily amenable with off-the-shelf instrumentation. To overcome these challenges, we have designed a platform that simultaneously aligns type I COL fibrils under mild shear flow and builds up the material through layer-by-layer assembly. We explored the mechanisms propagating fibril alignment, targeting experimental variables such as shear rate, viscosity, and time. Coarse-grained molecular dynamics simulations were also employed to help understand how initial reaction conditions including chain length, indicative of initial polymerization, and chain density, indicative of concentration, in the reaction environment impact fibril growth and alignment. When taken together, the mechanistic insights gleaned from these studies inspired the design, iteration, fabrication, and then customization of the fibrous collagenous materials, illustrating a platform material that can be readily adapted to future tissue engineering applications.
Background: Collagenous tissues are composed of precisely oriented, tightly packed collagen fibril bundles to confer the maximal strength within the smallest volume. While this compact form benefits mobility, it consequentially restricts vascularity and cell density to a minimally viable level in some regions. These tissues reside in a homeostatic state with an unstable equilibrium, where perturbations to structure or molecular milieu cause descension into a long-term compromised state. Several studies have shown that glycosaminoglycans are key molecules required for healthy tissue maintenance. Our long-term goal is to determine if glycosaminoglycans serve a critical function of stabilizing soluble monomeric collagen in the interstitial fluid that bathes tissue for immediate availability in tissue development and repair in vivo. Materials and Methods: To test glycosaminoglycan and collagen interactions at the most fundamental level, we have explored the effect of the monosaccharides that populate the glycosaminoglycans of the extracellular matrix on collagen assembly kinetics, pre-established matrix stability, and collagen incorporation into a preassembled matrix. Results: Results showed that monosaccharides increased the threshold concentration required for spontaneous polymerization by at least three orders of magnitude. When the monosaccharides were introduced to a pre-existing collagen network, fibrillar dissociation was undetectable. Fluorescent-labeling studies illustrated that in the presence of the saccharide solution, soluble collagen maintains the functional capacity to integrate into a pre-existing network. Conclusion: This work demonstrates a feasible role for glycosaminoglycans in supporting tissue remodeling and highlights the potential importance of age-related deterioration of glycosaminoglycan biosynthesis in reference to the homeostasis of collagen-based tissues.
The aim of this research is to survey preferences in the astronomy and astrophysics community as they relate to the next decade of NASA. Preferences are key for understanding how decisions are made by individuals that could aid in projecting community preferences and likely outcomes. The study was performed using a survey methodology and evaluated preferences regarding the decadal survey by prioritizing space-based astrophysics missions and research activities. Thematic analysis was implemented to determine themes within participants' open survey responses. Our results show strong community preferences for observational astronomy and science versatility, capability, and scientific return for the upcoming decadal period. Moreover, our findings also show consensus among subgroups in the community. We elaborate on community preferences by presenting results on mission concepts, mission capabilities, and primary science that NASA should strategically invest in.
Efficiently manipulating and reproducing the collagen (COL) alignment in vitro remains challenging because many of the fundamental mechanisms underlying and guiding the alignment process are not known. We reconcile experiments...
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