Biology subjects

Dunlop, J. W. C.

Publications and source records attributed to Dunlop, J. W. C..

4 recordsLinked to original sources

bioRxiv2026

Surface curvature promotes coordinated extracellular matrix remodeling and mechanotransductive signaling during osteoblast adaptation

Background: Substrate curvature is an important biophysical cue regulating cell behavior through mechanotransduction. However, how three-dimensional curvature regulates osteoblast transcriptional adaptation remains poorly understood. We investigated the temporal transcriptional response of pre-osteoblastic cells to defined substrate curvature. Methods: Murine MC3T3-E1 pre-osteoblasts were cultured on three-dimensional polydimethylsiloxane capillary bridges or flat substrates for 7 and 23 days to investigate the effects of surface curvature on gene expression. A genome-wide transcriptomic approach was employed to comprehensively characterize differential gene expression, followed by a focused analysis of selected biological pathways, including osteogenic signaling, extracellular matrix (ECM) organization, cell-matrix adhesion, cytoskeletal regulation, and mechanosensitive signaling. Results: Substrate curvature induced pronounced, time-dependent transcriptional changes. At day 7, curved substrates activated immediate-early and stress-responsive genes, including Egr1, Egr2, Fos, Junb, and Nr4a1. By day 23, the response shifted toward ECM remodeling, receptor-mediated signaling, and structural adaptation, including increased expression of Ankrd1, Ereg, Serpine1, and Plaur. Despite these changes, canonical osteogenic transcription factors, including Runx2, Cbfb, Osx/Sp7, and Atf4, showed limited alterations. In contrast, BMP, WNT, FGF, and Notch signaling, ECM components, integrins, and actin-associated genes were dynamically regulated, whereas Piezo1, Piezo2, and most septins remained comparatively stable. Conclusions: Substrate curvature regulates osteoblast transcriptional adaptation primarily through coordinated changes in ECM organization, cell-matrix interactions, cytoskeletal architecture, and signaling networks rather than reprogramming the canonical osteogenic transcriptional machinery.

cell biology↗

bioRxiv2025

Cortical Tension Links Curvature to Tissue Growth in the Cellular Potts Model

The growth of biological tissue is sensitive to the physical properties of the environment. For example, the growth rate of contractile tissue under geometric confinement is proportional to local curvature as a result of tissue surface tension. It is not known how local cell behavior is coordinated to give rise to such behavior. Here, we use computer simulations based on the Cellular Potts Model (CPM) to investigate the role of cell adhesion and cortical contractility for curvature-dependent tissue growth. Our results show that tension-dependent local proliferation leads to the observed macroscopic curvature-driven growth kinetics via tissue surface tension, independent of soluble growth factors.

biophysics↗

bioRxiv2023

Twisted plywood-like tissue formation in vitro. Does curvature do the twist?

Little is known about the contribution of 3D surface geometry on the development of multi-layered tissues containing fibrous extracellular matrix components such as those found in bone. Here we elucidate the role of curvature in the formation of chiral, twisted plywood-like structures. Tissues consisting of murine pre-osteoblast cells (MC3T3-E1) were grown on 3D scaffolds with constant mean curvature and negative Gaussian curvature for up to 32 days. Using 3D fluorescence microscopy, the influence of surface curvature on actin stress-fiber alignment and chirality was investigated. To gain mechanistic insights, also MC3T3-E1 cells deficient in nuclear A-type lamins or treated with drugs targeting cytoskeleton proteins were used in our study. We find that wild type cells grow multilayered tissue with fibers predominantly aligned along directions of negative curvature, but where subsequent layers twist in orientation with respect to older tissues with time. Fiber orientation is conserved below the tissue surface thus creating a twisted plywood like material. We further show that this directional organization strongly depends on structural components of the cells (A-type lamins, actin and myosin). Our data indicate the importance of substrate curvature in the formation of 3D tissues and provides new insights into the emergence of chirality. Significance StatementBiological tissues (like compact bone) often consist of multiple fibrous layers which are staggered with a twisting angle relative to each other, thereby improving mechanical performance. The underlying principles of how such tissues are formed and what determines the fiber direction are still debated. Here we report the formation of a twisted plywood-like tissue grown in vitro on constant mean and negative Gaussian curvature substrates and present evidence that for tissue consisting of pre-osteoblast like cells, surface curvature is a main determinant for fiber orientation.

biophysics↗

bioRxiv2018

Surface tension determines tissue shape and growth kinetics

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 ...

biophysics↗