<p>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 (<i>e.g.</i> 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
<i>in vivo</i> conditions. There is a need for the mechanical characterization
of the ECM networks formed by proteins synthesized <i>in vivo</i> while in
their native configuration. </p>
<p>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 <i>in situ</i>. 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 <i>in situ</i>. 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.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12736370 |
| Date | 31 July 2020 |
| Creators | Andrea Acuna (9183650) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/Characterizing_the_mechanical_behavior_of_extracellular_matrix_networks_in_situ/12736370 |
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