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Characterizing the mechanical behavior of extracellular matrix networks in situ

thesis
posted on 31.07.2020 by Andrea Acuna

The extracellular matrix (ECM) plays a significant role in defining the mechanical properties of biological tissues. The proteins, proteoglycans, and glycosaminoglycans that constitute the ECM are arranged into highly organized structures (e.g. fibrils and networks). Cellular behavior is affected by the stiffness of the microenvironment and influenced by the composition and organization of the ECM. Mechanosensing of ECM stiffness by cells occurs at the fibrillar (mesoscale) level between the single molecule (microscale) and the bulk tissue (macroscale) levels. However, the mechanical behavior of ECM proteins at the mesoscale are not well defined. Thus, better understanding of the ECM building blocks responsible for functional tissue assembly is critical in order to recapitulate in vivo conditions. There is a need for the mechanical characterization of the ECM networks formed by proteins synthesized in vivo while in their native configuration.

To address this gap, my goals highlighted in this dissertation were to develop appropriate experimental and computational methodologies and investigate the 3D organization and mechanical behavior of ECM networks in situ. The ECM of developing mouse tissues was used as a model system, taking advantage of the low-density networks present at this stage. First, we established a novel decellularization technique that enhanced the visualization of ECM networks in soft embryonic tissues. Based on this technique, we then quantified tissue-dependent strain of immunostained ECM networks in situ. Next, we developed mesoscale and macroscale testing systems to evaluate ECM networks under tension. Our systems were used to investigate tendon mechanics as a function of development, calculating tangent moduli from stress - strain plots. Similarly, we characterized ECM network deformation while uniaxially loading embryonic tissues, since this testing modality is ideal for fibril and network mechanics. Taken together, this information can facilitate the fabrication of physiologically relevant scaffolds for regenerative medicine by establishing mechanical guidelines for microenvironments facilitate functional tissue assembly.

Funding

Defining the mechanical link that unites the musculoskeletal system during limb development

National Center for Complementary and Integrative Health

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Biomechanical Influence of ECM Remodeling on the Developing Enthesis

National Institute of Arthritis and Musculoskeletal and Skin Diseases

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Multiscale Mechanobiology of Growth and Remodeling During Wound Healing

Directorate for Engineering

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History

Degree Type

Doctor of Philosophy

Department

Biomedical Engineering

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Sarah Calve

Advisor/Supervisor/Committee co-chair

Craig J. Goergen

Additional Committee Member 2

Adrian Buganza Tepole

Additional Committee Member 3

Abigail Cox

Licence

Exports