Biology subjects

Bordoloi, A. D.

Publications and source records attributed to Bordoloi, A. D..

4 recordsLinked to original sources

bioRxiv2025

Inter-Spheroid Proximity and Matrix Remodeling Determine CAF-Mediated Cancer Cell Invasion

Breast cancer is the most commonly diagnosed malignancy worldwide, with molecular subtypes following distinct clinical trajectories. While Luminal A breast cancers are typically indolent, a subset enriched in -smooth muscle actin (-SMA)-positive cancer-associated fibroblasts (CAFs) exhibits aggressive behavior, facilitating tumor invasion. However, the biophysical mechanisms by which CAFs drive invasion and extracellular matrix (ECM) remodeling remain unclear. Furthermore, the temporal and spatial dynamics of CAF interactions with the collagen matrix and cancer cell spheroids remain unknown, raising the question of whether these processes follow a deterministic sequence or occur stochastically. To address this, we conduct histological analysis of Luminal A tumors, revealing variation in CAF, cancer cell, and ECM organization at tumor boundaries. To assess the impact of CAF on cancer cell invasion, we use a 3D in-vitro model co-embedding 19TT breast CAF and MCF7 luminal breast cancer spheroids within a three-dimensional (3D) collagen-I hydrogel and perform time-lapse imaging. We demonstrate that inter-spheroid distance critically determines 19TT CAF-induced MCF7 spheroid behavior. Furthermore, we show that CAF-mediated collagen matrix remodeling and degradation precedes MCF7 spheroid disruption and is critical in promoting cancer cell spheroid expansion and cell dissemination. While broad-spectrum matrix metalloproteinase inhibition suppresses CAF-driven collagen degradation and MCF7 spheroid expansion, it does not prevent ECM remodeling, CAF migration, or single-cell dissemination of cancer cell spheroids. Furthermore, a complementary heterospheroid model reveals similar ECM remodeling and invasion dynamics despite altered cellular arrangement of cancer cells and CAFs. These findings enhance our understanding of the relationship between CAF activity and collagen matrix remodeling processes that promote cancer cell invasion, providing insights into the potential therapeutic benefits of targeting CAFs in breast cancer treatment.

cancer biology↗

bioRxiv2025

Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion

Collagen networks form the structural backbone of the extracellular matrix in both healthy and cancerous tissues, exhibiting nonlinear mechanical properties that crucially regulate tissue mechanics and cell behavior. Here, we investigate how the presence of invasive breast cancer cells (MDA-MB-231) influences the polymerization kinetics and mechanics of collagen networks using bulk shear rheology and rheo-confocal microscopy. We show that embedded cancer cells delay the onset of collagen polymerization due to volume exclusion effects. During polymerization, the cells (at 4% volume fraction) cause an unexpected time-dependent softening of the network. We show that this softening effect arises from active remodeling via adhesion and contractility rather than from proteolytic degradation. At higher cell volume fractions, the dominant effect of the cells shifts to volume exclusion, causing a two-fold reduction of network stiffness. Additionally, we demonstrate that cancer cells suppress the characteristic stress-stiffening response of collagen. This effect (partially) disappears when cell adhesion and contractility are inhibited, and it is absent when the cells are replaced by passive hydrogel particles. These findings provide new insights into how active inclusions modify the mechanics of fibrous networks, contributing to a better understanding of the role of cells in the mechanics of healthy and diseased tissues like invasive tumors.

biophysics↗

bioRxiv2024

Linking metastatic potential and viscoelastic properties of breast cancer spheroids via dynamics compression and relaxation in microfluidics

The growth and invasion of solid tumors are associated with changes in their viscoelastic properties, influenced by both internal cellular factors and physical forces in the tumor microenvironment. Due to the lack of a comprehensive investigation of tumor tissue viscoelasticity, the relationship between such physical properties and cancer malignancy remains poorly understood. Here, the viscoelastic properties of breast cancer spheroids, 3D (in vitro) tumor models, are studied in relation to their metastatic potentials by imposing controlled, dynamic compression within a microfluidic constriction, and subsequently monitoring the relaxation of the imposed deformation. By adopting a modified Maxwell model to extract viscoelastic properties from the compression data, the benign (MCF-10A) spheroids are found to have higher bulk elastic modulus and viscosity compared to malignant spheroids (MCF-7 and MDA-MB-231). The relaxation is characterized by two timescales, captured by a double exponential fitting function, which reveals a similar fast rebound for MCF-7 and MCF-10A. Both the malignant spheroids exhibit similar long-term relaxation and display residual deformation. However, they differ significantly in morphology, particularly in intercellular movements. These differences between malignant spheroids are demonstrated to be linked to their cytoskeletal organization, by microscopic imaging of F-actin within the spheroids, together with cell-cell adhesion strength.

biophysics↗

bioRxiv2023

Spatial structure, chemotaxis and quorum sensing shape biomass accumulation in complex systems

Biological tissues, sediments, or engineered systems are spatially structured media with a tortuous and porous structure that host the flow of fluids. Such complex environments can influence the spatial and temporal colonization patterns of bacteria by controlling the transport of individual bacterial cells, the availability of resources, and the distribution of chemical signals for communication. Yet, due to the multi-scale structure of these complex systems, it is hard to assess how different biotic and abiotic properties work together to control the accumulation of bacterial biomass. Here, we explore how flow mediated interactions allow the gut commensal Escherichia coli to colonize a porous structure that is composed of heterogenous dead-end pores (DEPs) and connecting percolating channels, i.e. transmitting pores (TPs), mimicking the structured surface of mammalian guts. We find that in presence of flow, gradients of the quorum sensing (QS) signaling molecule autoinducer-2 (AI-2) promote E. coli chemotactic accumulation in the DEPs. In this crowded environment, the combination of growth and cell-to-cell collision favors the development of suspended bacterial aggregates. This results in hot-spots of resource consumption, which, upon resource limitation, triggers the mechanical evasion of biomass from glucose and oxygen depleted DEPs. Our findings demonstrate that microscale medium structure and complex flow coupled with bacterial quorum sensing and chemotaxis control the heterogenous accumulation of bacterial biomass in a spatially structured environment, such as villi and crypts in the gut or in tortuous pores within soil and filters.

microbiology↗