Collagen stiffness modulates MDA-MB231 cell metabolism through adhesion-mediated contractility

Mah, Emma J.; McGahey, Gabrielle E.; Yee, Albert F.; Digman, Michelle A.

doi:10.1101/272948

Cited by 3 publications

(4 citation statements)

References 67 publications

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“…Conversely, for post-metastatic MDA-MB-231 spheroids, cells at the core are larger, more variable in shape, and more migratory with respect to their MCF-10A counterparts, while the periphery is highly sensitive to changes in collagen density (Figures 3 and 4). Compared to MCF-10A cells, they also generate higher traction forces (The PS-OC Network et al, 2013) and are more metabolically responsive (Mah et al, 2018). Together, this constellation of structural, migratory, mechanical, and metabolic factors is consistent with the existence of an effective temperature, T eff , that is spatially heterogeneous.…”

Section: Discussionmentioning

confidence: 85%

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

et al. 2021

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Summary It is well established that the early malignant tumor invades surrounding extracellular matrix (ECM) in a manner that depends upon material properties of constituent cells, surrounding ECM, and their interactions. Recent studies have established the capacity of the invading tumor spheroids to evolve into coexistent solid-like, fluid-like, and gas-like phases. Using breast cancer cell lines invading into engineered ECM, here we show that the spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front. Using a computational approach, we further show that these patterns are captured by a novel jamming phase diagram. We suggest that non-equilibrium phase separation based upon jamming and unjamming transitions may provide a unifying physical picture to describe cellular migratory dynamics within, and invasion from, a tumor.

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Section: Discussionmentioning

confidence: 85%

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

et al. 2021

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“…Studies suggesting roles for cholesterol in cell membrane stiffness and tension have been conducted; however, further investigation would be required to validate these theories. Interestingly, the data variability of each cell consistently decreases as cell stiffness increases, showing the smallest variance in HaCaT (10 kPa) and L929 (4 kPa) and larger variance for the softer MG63 and MSCs (0.3–0.8 kPa) respectively (see Table S4 in the Supporting Information for tabulated values). This is indicative of the inherent heterogeneity which is known to be more prevalent in softer cell types (i.e., MSCs) than stiffer ones (i.e., HaCaT).…”

Section: Discussionmentioning

confidence: 99%

“…They were HaCaT (human keratinocytes), L929 (mouse fibroblast), MSCs (mesenchymal stromal cells, human bone marrow‐derived primary cells), and MG63 (mouse osteosarcoma). The selected cells represent not only species and source tissue variability but also vast differences in predicted cell stiffness values, ranging from 0.8 kPa (MSCs) to 10 kPa (HaCaT) to better understand the impact of acoustic exposure on cell heterogeneity. Experiments we have performed show no significant differences in nuclear morphology and proliferation rates across all cell types and conditions studied.…”

Section: Introductionmentioning

confidence: 99%

Cell Adhesion, Morphology, and Metabolism Variation via Acoustic Exposure within Microfluidic Cell Handling Systems

et al. 2019

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As the applications of this technology are focused within the clinical and life sciences, a thorough understanding of the associated biological impact imposed by these manipulation techniques is necessary.The desire to manipulate suspended matter within microfluidic systems has inspired a range of techniques both passive [5,19,20] and active. [21,22] Passive approaches rely heavily on the geometry of the microfluidic channels and inertial forces. Flow profiles are altered by the introduction of sudden expansions and contractions, weirs and pillars to impede and divert the flow into desired streamlines. This reliance on the resultant flow profile restricts the flexibility of the chip, being single task specific. In contrast, active methods are significantly more robust, capable of on-demand actuation and offer the ability to change functionality ad-hoc, leading to an increased selectivity. To this end, a range of active methods have been developed using magnetic, [23,24] optical, [25,26] electrical [16,27] and acoustic [28][29][30] excitation.Acoustofluidics is the use of acoustic forces to manipulate suspended matter within microfluidics, [31,32] and has the advantage of uniquely combining ease of on-chip integration and simple, yet dextrous establishment of force fields in a noncontact manner. [29,33,34] As a direct result, it has been extensively used to capture, [33,35] pattern, [36][37][38] and sort particles, [15,34,39] cell sonoporation, [40] synthesize nanomaterials, [41] as well as to mix fluids. [42,43] Although acoustofluidics has been widely accepted as a biocompatible technique, substantiated with cell viability studies; [44][45][46][47][48] there have been no extensive viability studies at elevated frequencies (30-600 MHz). Indeed, typically studies are corroborated with a single viability method, most commonly live/dead staining, [6,[49][50][51] or trypan blue exclusion [52,53] and in some instances proliferation studies (MTT). [36] In contrast to these singular approaches, in passive microfluidic systems in which cells are predominantly subjected to shear forces arising from the flow field, a wide range of multifaceted cell viability studies [54] have been conducted showing, for example, sheardependent regulation of the von Willebrand factor of human umbilical vein endothelial cells [55] and the potential for circulating tumor cell apoptosis at high shear levels. [56] This lack of biological knowledge may result in potential unrecognized adverse effects (i.e., "false positives"), or Acoustic fields are capable of manipulating biological samples contained within the enclosed and highly controlled environment of a microfluidic chip in a versatile manner. The use of acoustic streaming to alter fluid flows and radiation forces to control cell locations has important clinical and life science applications. While there have been significant advances in the fundamental implementation of these acoustic mechanisms, there is a considerable lack of understanding of the associated biological effects on cells. ...

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“…). Those types of collagen dominate the tumour microenvironment and are procarcinogenic by regulating tumour density and stiffness . Increased density of type I collagen in tumour stroma is associated with decreased dispersion of anticancer drugs within the tumour that reduced their bioavailability and attenuates their absorption by tumour cells, thus diminishing their therapeutic effect .…”

Section: Reactive Stroma In Normal and Cancer Wound Healingmentioning

confidence: 99%

Stroma in normal and cancer wound healing

et al. 2019

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It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self‐limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets.

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Collagen stiffness modulates MDA-MB231 cell metabolism through adhesion-mediated contractility

Cited by 3 publications

References 67 publications

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

Cell Adhesion, Morphology, and Metabolism Variation via Acoustic Exposure within Microfluidic Cell Handling Systems

Stroma in normal and cancer wound healing

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