Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/456228

Surface tension determines tissue shape and growth kinetics

Ehrig, S.·Bidan, C. M.·West, A.·Jacobi, C.·Lam, K.·Kollmannsberger, P.·Petersen, A.·Tomancak, P.·Kommareddy, K.·Fischer, F. D.·Fratzl, P.·Dunlop, J. W. C.
View original source ↗Export metadata ↓

Abstract

The growth of tissue is an essential process controlling morphogenesis and regeneration of organs [1]. In general tissue forming cells are interactive and motile [2], which can give rise to emergent physical properties such as viscous fluid behaviour as has been shown for epithelial monolayers during embryogenesis [3, 4], and for cell-agglomerates [5] with a measurable surface tension [6]. However, the mechanical integrity of tissues is provided by extracellular matrices (ECM) that turn tissues into solids with well-defined elastic properties [7]. Paradoxically, it has been shown by in-vitro experiments that even osteoid-like tissue with large amounts of ECM grows according to rules reminiscent of fluid behavior [8, 9]. Motivated by this conundrum, we show here quantitatively, by constraining growing tissues to surfaces of con ...

Source connections

Explore related subjects

biophysicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ehrig, S., Bidan, C. M., West, A., Jacobi, C., Lam, K., Kollmannsberger, P., Petersen, A., Tomancak, P., Kommareddy, K., Fischer, F. D., Fratzl, P., Dunlop, J. W. C.. 2018-10-29. Surface tension determines tissue shape and growth kinetics. https://doi.org/10.1101/456228

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Growth-driven mechanical buckling as a mechanism of age-related tortuosity in human cerebral arteries

Human cerebral arteries become increasingly, sometimes abnormally, winding with age, but the mechanical basis of this change remains incompletely understood. To examine how arterial bends form and what sets their spacing, we modeled a cerebral artery as a slender elastic vessel supported by surrounding tissue. The distance between its ends remains constant, and the vessel can bend only in a plane tangent to the brain surface. As its natural length increases, axial compression builds until the vessel buckles. Bending partly relieves the compression, and the resulting waves grow in amplitude as elongation continues. Arterial bending stiffness and tissue support determine the wavelength, which is much larger than and proportional to vessel diameter, with comparatively weak dependence on other parameters. Numerical simulations captured a pre-buckling phase, rapid amplification of waves, and slow post-buckling growth during continued elongation. We evaluated these predictions using three-dimensional centerlines of cerebral arteries reconstructed from magnetic resonance angiography in healthy adults. Older age was associated with greater arterial length and excess-length ratio. For arterial waves oriented mostly parallel to the brain surface, wavelength increased with vessel diameter. Both this relationship and the observed wavelength-to-diameter ratio were consistent with model predictions. However, wave amplitude was not significantly associated with age. Overall, the modeling and imaging results support growth-driven buckling and post-buckling deformation under spatial constraint as a plausible mechanical explanation for age-related cerebral arterial tortuosity. This framework links vascular aging to growth-driven instability and pattern formation, with potential applications to diseased arteries beyond the brain.

biophysics↗
bioRxiv2026

The binding landscape of Ras/effector interactions provides insights on Ras switching and oncogenesis

Protein-protein interactions (PPIs) regulate essential cellular processes, yet the evolutionary principles that shape their specificity, adaptability, and dysregulation in disease remain poorly understood. Here, we investigate the evolution of a signaling PPI between the small GTPase Ras and its effector Nore1A, a tumor suppressor involved in Ras-mediated signaling. Ras acts as a molecular switch, engaging effectors in its GTP-bound active state and releasing them after GTP hydrolysis, whereas oncogenic mutations such as G12D lock Ras in the active state, promoting aberrant signaling in cancer. Using yeast surface display, deep mutational scanning, and data normalization, we systematically mapped the Ras/Nore1A binding landscape under different physiological and oncogenic states. We generated and screened $\sim$33,000 Nore1A single and double mutants against RasWT and RasG12D in both GTP- and GDP-bound states. Our data revealed that most Nore1A mutations produce small-to-moderate decrease in Ras affinity, while a small number of substitutions enhance affinity. Unexpectedly, GTP hydrolysis causes minimal remodeling of the interaction landscape. Conversely, the oncogenic RasG12D mutation reshapes the binding landscape, revealing many Nore1A variants with enhanced and selective affinity for mutant Ras. Molecular dynamics (MD) simulations of Nore1A-Ras variant complexes suggest that the non-optimality of the Nore1A/RasG12D binding landscape arises, in part, from the greater intrinsic flexibility of RasG12D and the pronounced reduction in flexibility induced by affinity-enhancing Nore1A mutations. These findings demonstrate that disease-associated mutations can create new evolutionary trajectories in signaling PPIs by changing interaction dynamics and provide a framework for engineering selective protein-based inhibitors targeting oncogenic Ras variants.

biophysics↗
bioRxiv2026

Lipidic α-synuclein fibrils catalyze the formation of pathological mature fibrils

The aggregation of -synuclein into amyloid fibrils is a hallmark of a collection of neurodegenerative diseases termed synucleinopathies, including Parkinson's disease (PD). Interactions between -synuclein and lipid membranes modulate -synuclein aggregation and can produce protofibril structures consisting of both protein and lipid, termed lipidic fibrils. These lipidic fibrils can mature into mature fibrils, which resemble ex vivo fibrils extracted from Lewy bodies found in post-mortem brain samples of PD patients. Here, through the combination of experiments and kinetic theory, we study the influence of lipids and lipidic fibrils on the formation of mature fibrils. We find that lipidic fibrils catalyze mature fibril formation via a heterogeneous primary nucleation mechanism, which lowers the activation energy barrier of mature fibril formation relative to lipid-independent primary nucleation. The final stage of the reaction is governed by mature fibril elongation becoming limited by the rate at which protein monomers dissociate from the metastable lipidic fibrils, confirming that fibrils form in order of stability following Ostwald's Rule of Stages. This mechanism is validated using the small molecule inhibitor ambroxol, which selectively suppresses the formation of lipidic fibrils and in this manner shifts the aggregation kinetics to the slow, lipid-independent pathway. Taken together, these findings reveal that lipidic fibrils act as on-pathway intermediates and accelerate the aggregation of mature fibrils, which could provide a quantitative framework to design novel therapeutic strategies to inhibit pathological -synuclein aggregation.

biophysics↗