Biology subjects

Madzvamuse, A.

Publications and source records attributed to Madzvamuse, A..

4 recordsLinked to original sources

bioRxiv2026

Basement membrane turnover drives filopodial protease-independent invasion

The basement membrane is a specialised nanoporous extracellular matrix mainly composed of collagen IV fibres and laminins. As collagen IV fibres form covalent cross-links, cells cannot freely cross it. Basement membrane breaching marks the transition from in situ to invasive carcinoma, commonly attributed to protease activity. Yet, recent data show that tumour cells can cross basement membranes through protease-independent mechanisms. Experimental evidence suggests that filopodia can play an active role in pore enlargement in extracellular matrices by generating plastic mechanical deformation. Moreover, plasticity can be regulated by covalent cross-link concentration, which we hypothesise can be responsive to collagen IV turnover, thus generating transient weak spots. To test this, we developed a quantitative, biophysical mathematical model describing the interaction between a tumour-cell cluster and a basement membrane using relevant biological assumptions and parameters. The cluster is represented as an evolving, energetic surface and the basement membrane is described as a set of points representing active and inactive links. Simulations show that synchronisation of collagen IV turnover coupled with filopodium extension drives pore enlargement, providing a mechanistic basis for protease-independent invasion. Consistent with experiments, simulations identify two complementary filopodium groups: one driving global degradation and the other promoting local pore enlargement.

biophysics↗

bioRxiv2025

A geometric-surface PDE model for cell-nucleus translocation through confinement

Understanding how cells migrate through confined environments is crucial for elucidating fundamental biological processes, including cancer invasion, immune surveillance, and tissue morphogenesis. The nucleus, as the largest and stiffest cellular organelle, often limits cellular deformability, making it a key factor in migration through narrow pores or highly constrained spaces. In this work, we introduce a geometric surface partial differential equation (GS-PDE) model in which the cell plasma membrane and nuclear envelope are described as evolving energetic closed surfaces governed by force-balance equations. We replicate the results of a biophysical experiment, in which a microfluidic device is used to impose compressive stresses on cells by driving them through narrow microchannels under a controlled pressure gradient. The model is validated by reproducing cell entry into the microchannels. A parametric sensitivity analysis highlights the dominant influence of specific parameters, whose accurate estimation is essential to faithfully capture the experimental setup. We found that surface tension and confinement geometry emerge as key determinants of translocation efficiency. Although tailored to this specific setup for validation purposes, the framework is sufficiently general to be applied to a broad range of cell mechanics scenarios, providing a robust and flexible tool for investigating the interplay between cell mechanics and confinement. It also offers a solid foundation for future extensions integrating more complex biochemical processes such as active confined migration. Author summaryCells often migrate through very narrow spaces in tissues, a process critical for cancer invasion, immune surveillance, and tissue development. In particular, the stiffness of the nucleus, the largest and most rigid organelle, can limit migration through tight pores. In this study, we present a mathematical model describing the motion of a cell and its nucleus through a microchannel during cell translocation, using a geometric formulation based on surface partial differential equations. The model is general and applicable to a variety of scenarios involving confined cell transport. The model is validated by reproducing key experiments on cell translocation through narrow microchannels. The framework incorporates essential surface features, including mechanical responses, bending rigidity, and surface tension. Sensitivity analysis highlights surface tension and channel geometry as the parameters that most strongly influence translocation. Overall, the model provides new insights into the mechanics of confined cell transport, grants access to cellular quantities that are difficult to measure experimentally, such as cell and nucleus areas, perimeters, and stresses, and establishes a foundation for future extensions incorporating more complex biochemical processes.

biophysics↗

bioRxiv2025

Quantifying the organization and dynamics of M. smegmatis morphology from Long-Term Time-Lapse Atomic Force Microscopy

The rod shaped Mycobacterium smegmatis displays complex cell surface morphology, characterized by wave-form cell surface features and driven by asymmetric growth dynamics. To systematically analyze these morphological variations, we developed a comprehensive computational pipeline for automated processing of Long-Term Time-Lapse Atomic Force Microscopy (LTTL-AFM) images of M. smegmatis cells cultured in axenic conditions of growth and stress. Upon running the pipeline to produce large enough datasets of single cell height profiles, we identify and statistically study key features that govern cell surface morphology: We confirm that M. smegmatis cells undergo bi-phasic, asymmetric pole growth with constant elongation rate at the old pole and a shift in the rate of elongation after a lag phase at the new pole. Stable wave-form cell surface peaks and troughs propagate along the long axis of the cell, which emerge as a result of polar elongation. Backtracking in time from cell division, we detect that division-site selection occurs at the wave-trough nearest mid-cell. To reproduce the fundamental cell features observed, we introduced a reaction-diffusion mathematical model on an evolving one-dimensional surface. Our simulations indicate that the dynamic manifestation of wave-form cell surface morphology in M. smegmatis can be explained by the interaction of as few as two "chemical species", providing a plausible theoretical basis for how molecular determinants may functionally control wave-form morphology in pole-growing bacteria.

cell biology↗

bioRxiv2023

A bulk-surface moving-mesh finite element method for modelling cell migration pathways

Cell migration is an ubiquitous process in life that is mainly triggered by the dynamics of the actin cytoskeleton and therefore is driven by both mechanical properties and biochemical processes. It is a multistep process essential for mammalian organisms and is closely linked to development, cancer invasion and metastasis formation, wound healing, immune response, tissue differentiation and regeneration, and inflammation. Experimental, theoretical and computational studies have been key to elucidate the mechanisms underlying cell migration. On one hand, rapid advances in experimental techniques allow for detailed experimental measurements of cell migration pathways, while, on the other, computational approaches allow for the modelling, analysis and understanding of such observations. Here, we present a computational framework coupling mechanical properties with biochemical processes to model two-dimensional cell migration by considering membrane and cytosolic activities that may be triggered by external cues. Our computational approach shows that the numerical implementation of the mechanobiochemical model is able to deal with fundamental characteristics such as: (i) membrane polarisation, (ii) cytosolic polarisation, and (iii) actin-dependent protrusions. This approach can be generalised to deal with single cell migration through complex non-isotropic environments, both in 2- and 3-dimensions. Author summaryWhen a single or group of cells follow directed movement in response to either chemical and/or mechanical cues, this process is known as cell migration. It is essential for many biological processes such as immune response, embryogenesis, gastrulation, wound repair, cancer metastasis, tumour invasion, inflammation and tissue homeostasis. However, aberrant or defects in cell migration lead to various abnormalities and life-threatening medical conditions [1-4]. Increasing our knowledge on cell migration can help abate the spread of highly malignant cancer cells, reduce the invasion of white cells in the inflammatory process, enhance the healing of wounds and reduce congenital defects in brain development that lead to mental disorders. In this study, we present a computational framework that allows us to couple mechanical properties with biochemical signalling processes to study long time behaviour of single cell migration (either directed or random). The novelty is that the evolution law for the velocity (also known as the flow or material velocity) is described by a biomechanical force balance model posed inside the cell and this in turn is driven by the actomyosin spatiotemporal model (following the classical theory of reaction-diffusion) which is responsible for force generation as described in many experimental works [2, 5, 8, 10, 11]. Hence, our modelling approach is based on a new mathematical formalism of bulk-surface partial differential equations coupled with a novel adaptive moving-mesh finite element method to allow for significant cell deformations during migration. The approach set premises to study cell migration through complex non-isotropic environments, thereby giving biologists a predictive tool for modelling cell migration.

biophysics↗