bims-ecemfi 2025-04-06 papers

Acta Biomater. 2025 Apr 01. pii: S1742-7061(25)00241-7. [Epub ahead of print]

Material properties of the embryonic small intestine during buckling morphogenesis.

Jenny Gao, Lucia Martin, Elise A Loffet, Raphael Bertin, John F Durel, Panagiotis Oikonomou, Nandan L Nerurkar.

During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops. The wavelength and curvature of these loops are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood. STATEMENT OF SIGNIFICANCE: : The functional form of adult organs is established during embryogenesis through the action of physical forces on tissues with precise material properties. Despite this, however, biological control of material properties during embryogenesis is poorly understood. Focusing on the small intestine, we identified elastic fibers - rather than oriented smooth muscle - as defining bending stiffness, prescribing the lengthy intestine to be buckled precisely into compact loops for proper placement within the body cavity. We revealed a role for elastin in storing elastic energy during cell contraction, highlighting a potential role for elastin in gut motility through the ability to resist cyclic deformations associated with peristalsis. These results provide insights into intestinal development and adult function, and highlight elastin's diverse roles during organogenesis.

Keywords: biomechanics; elastin; extracellular matrix; gut looping; smooth muscle

DOI: https://doi.org/10.1016/j.actbio.2025.03.055

bioRxiv. 2025 Mar 19. pii: 2025.03.18.643983. [Epub ahead of print]

Sp1 mechanotransduction regulates breast cancer cell invasion in response to multiple tumor-mimicking extracellular matrix cues.

Abhishek Sharma, Rowan F Steger, Jen M Li, Jane A Baude, Kellie A Heom, Siddharth S Dey, Ryan S Stowers.

Breast cancer progression is marked by extracellular matrix (ECM) remodeling, including increased stiffness, faster stress relaxation, and elevated collagen levels. In vitro experiments have revealed a role for each of these factors to individually promote malignant behavior, but their combined effects remain unclear. To address this, we developed alginate-collagen hydrogels with independently tunable stiffness, stress relaxation, and collagen density. We show that these combined tumor-mimicking ECM cues reinforced invasive morphologies and promoted spheroid invasion in breast cancer and mammary epithelial cells. High stiffness and low collagen density in slow-relaxing matrices led to the greatest cell migration speed and displacement. RNA-seq revealed Sp1 target gene enrichment in response to both individual and combined ECM cues, with a greater enrichment observed under multiple cues. Notably, high expression of Sp1 target genes upregulated by fast stress relaxation correlated with poor patient survival. Mechanistically, we found that phosphorylated-Sp1 (T453) was increasingly located in the nucleus in stiff and/or fast relaxing matrices, which was regulated by PI3K and ERK1/2 signaling, as well as actomyosin contractility. This study emphasizes how multiple ECM cues in complex microenvironments reinforce malignant traits and supports an emerging role for Sp1 as a mechanoresponsive transcription factor.

DOI: https://doi.org/10.1101/2025.03.18.643983

bioRxiv. 2025 Mar 21. pii: 2024.11.05.622090. [Epub ahead of print]

Critical Cell Spacing Drives Phase Transition in Matrix-Mediated Tissue Condensation.

Xiangjun Peng, Yuxuan Huang, Wenyu Kong, Yanan Du, Elliot L Elson, Xi-Qiao Feng, Guy M Genin.

Biological tissues exhibit phase transitions governed by mechanical feedback between cells and their extracellular matrix (ECM). We demonstrate through bio-chemo-mechanical modeling that this emergent behavior arises from competing physical effects: increasing matrix stiffness enhances individual cell activation while simultaneously weakening long-range mechanical communication. This competition establishes a critical cell spacing threshold (80-160 µ m) that precisely matches experimental observations across diverse cell types and collagen densities. Our model reveals that the critical stretch ratio at which fibrous networks transition from compliant to strain-stiffening governs this threshold through the formation of tension bands between neighboring cells. These tension bands create a mechanical percolation network that drives the collective phase transition in tissue behavior. Our model explains how fibrous architecture controls emergent mechanical properties in biological systems and offers insight into both the physics of fiber-reinforced composite materials under active stress, and into potential mechanical interventions for fibrotic disorders.

DOI: https://doi.org/10.1101/2024.11.05.622090