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1. Toward Elucidating the Physiological Impacts of Residual Stresses in the Colorectum

   https://doi.org/10.1115/1.4051846  

   Zhao, Y.; Siri, S.; Feng, B.; Pierce, D. M. (January 2022, Journal of Biomechanical Engineering)

   Abstract Irritable bowel syndrome afflicts 10–20% of the global population, causing visceral pain with increased sensitivity to colorectal distension and normal bowel movements. Understanding and predicting these biomechanics will further advance our understanding of visceral pain and complement the existing literature on visceral neurophysiology. We recently performed a series of experiments at three longitudinal segments (colonic, intermediate, and rectal) of the distal 30 mm of colorectums of mice. We also established and fitted constitutive models addressing mechanical heterogeneity in both the through-thickness and longitudinal directions of the colorectum. Afferent nerve endings, strategically located within the submucosa, are likely nociceptors that detect concentrations of mechanical stresses to evoke the perception of pain from the viscera. In this study, we aim to: (1) establish and validate a method for incorporating residual stresses into models of colorectums, (2) predict the effects of residual stresses on the intratissue mechanics within the colorectum, and (3) establish intratissue distributions of stretches and stresses within the colorectum in vivo. To these ends we developed two-layered, composite finite element models of the colorectum based on our experimental evidence and validated our approaches against independent experimental data. We included layer- and segment-specific residual stretches/stresses in our simulations via the prestrain algorithm built into the finite element software febio. Our models and modeling approaches allow researchers to predict both organ and intratissue biomechanics of the colorectum and may facilitate better understanding of the underlying mechanical mechanisms of visceral pain. 

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2. The Macro- and Micro-Mechanics of the Colon and Rectum I: Experimental Evidence

   https://doi.org/10.3390/bioengineering7040130  

   Siri, Saeed; Zhao, Yunmei; Maier, Franz; Pierce, David M.; Feng, Bin (December 2020, Bioengineering)

   Many lower gastrointestinal diseases are associated with altered mechanical movement and deformation of the large intestine, i.e., the colon and rectum. The leading reason for patients’ visits to gastrointestinal clinics is visceral pain, which is reliably evoked by mechanical distension rather than non-mechanical stimuli such as inflammation or heating. The macroscopic biomechanics of the large intestine were characterized by mechanical tests and the microscopic by imaging the load-bearing constituents, i.e., intestinal collagen and muscle fibers. Regions with high mechanical stresses in the large intestine (submucosa and muscularis propria) coincide with locations of submucosal and myenteric neural plexuses, indicating a functional interaction between intestinal structural biomechanics and enteric neurons. In this review, we systematically summarized experimental evidence on the macro- and micro-scale biomechanics of the colon and rectum in both health and disease. We reviewed the heterogeneous mechanical properties of the colon and rectum and surveyed the imaging methods applied to characterize collagen fibers in the intestinal wall. We also discussed the presence of extrinsic and intrinsic neural tissues within different layers of the colon and rectum. This review provides a foundation for further advancements in intestinal biomechanics by synergistically studying the interplay between tissue biomechanics and enteric neurons. 

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3. The Macro- and Micro-Mechanics of the Colon and Rectum II: Theoretical and Computational Methods

   https://doi.org/10.3390/bioengineering7040152  

   Zhao, Yunmei; Siri, Saeed; Feng, Bin; Pierce, David M. (December 2020, Bioengineering)

   Abnormal colorectal biomechanics and mechanotransduction associate with an array of gastrointestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, diverticula disease, anorectal disorders, ileus, and chronic constipation. Visceral pain, principally evoked from mechanical distension, has a unique biomechanical component that plays a critical role in mechanotransduction, the process of encoding mechanical stimuli to the colorectum by sensory afferents. To fully understand the underlying mechanisms of visceral mechanical neural encoding demands focused attention on the macro- and micro-mechanics of colon tissue. Motivated by biomechanical experiments on the colon and rectum, increasing efforts focus on developing constitutive frameworks to interpret and predict the anisotropic and nonlinear biomechanical behaviors of the multilayered colorectum. We will review the current literature on computational modeling of the colon and rectum as well as the mechanical neural encoding by stretch sensitive afferent endings, and then highlight our recent advances in these areas. Current models provide insight into organ- and tissue-level biomechanics as well as the stretch-sensitive afferent endings of colorectal tissues yet an important challenge in modeling theory remains. The research community has not connected the biomechanical models to those of mechanosensitive nerve endings to create a cohesive multiscale framework for predicting mechanotransduction from organ-level biomechanics. 

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4. Relationships in Shark Skin: Mechanical and Morphological Properties Vary between Sexes and among Species

   https://doi.org/10.1093/icb/icad111  

   Hagood, Madeleine_E; Alexander, Joseph_R_S; Porter, Marianne_E (August 2023, Integrative And Comparative Biology)

   Synopsis Shark skin is a composite of mineralized dermal denticles embedded in an internal collagen fiber network and is sexually dimorphic. Female shark skin is thicker, has greater denticle density and denticle overlap compared to male shark skin, and denticle morphology differs between sexes. The skin behaves with mechanical anisotropy, extending farther when tested along the longitudinal (anteroposterior) axis but increasing in stiffness along the hoop (dorsoventral or circumferential) axis. As a result, shark skin has been hypothesized to function as an exotendon. This study aims to quantify sex differences in the mechanical properties and morphology of shark skin. We tested skin from two immature male and two immature female sharks from three species (bonnethead shark, Sphyrna tiburo; bull shark, Carcharhinus leucas; silky shark, Carcharhinus falciformis) along two orientations (longitudinal and hoop) in uniaxial tension with an Instron E1000 at a 2 mm s−1 strain rate. We found that male shark skin was significantly tougher than female skin, although females had significantly greater skin thickness compared to males. We found skin in the hoop direction was significantly stiffer than the longitudinal direction across sexes and species, while skin in the longitudinal direction was significantly more extensible than in the hoop direction. We found that shark skin mechanical behavior was impacted by sex, species, and direction, and related to morphological features of the skin. 

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5. Emergent depth-mechanosensing of epithelial collectives regulates cell clustering and dispersal on layered matrices

   https://doi.org/10.1073/pnas.2423875122  

   Yu, Hongsheng; Pathak, Amit (September 2025, Proceedings of the National Academy of Sciences)

   During wound healing, tumor growth, and organ formation, epithelial cells migrate and cluster in layered tissue environments. Although cellular mechanosensing of adhered extracellular matrices is now well recognized, it is unclear how deeply cells sense through distant matrix layers. Since single cells can mechanosense stiff basal surfaces through soft hydrogels of <10 μm thickness, here we ask whether cellular collectives can perform such “depth-mechanosensing” through thicker matrix layers. Using a collagen-polyacrylamide double-layer hydrogel, we found that epithelial cell collectives can mechanosense basal substrates at a depth of >100 μm, assessed by cell clustering and collagen deformation. On collagen layers with stiffer basal substrates, cells initially migrate slower while performing higher collagen deformation and stiffening, resulting in reduced dispersal of epithelial clusters. These processes occur in two broad phases: cellular clustering and dynamic collagen deformation, followed by cell migration and dispersal. Using a cell-populated collagen-polyacrylamide computational model, we show that stiffer basal substrates enable higher collagen deformation, which in turn extends the clustering phase of epithelial cells and reduces their dispersal. Disruption of collective collagen deformation, by either α-catenin depletion or myosin-II inhibition, disables the depth-mechanosensitive differences in epithelial responses between soft and stiff basal substrates. These findings suggest that depth-mechanosensing is an emergent property that arises from collective collagen deformation caused by epithelial cell clusters. This work broadens the conventional understanding of epithelial mechanosensing from immediate surfaces to underlying basal matrices, providing insights relevant to tissue contexts with layers of varying stiffness, such as wound healing and tumor invasion. 

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