​​How substrate properties influence cell behaviour?

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Cells sense their microenvironment by deforming the substrate via applying traction force and this information is then transduced to the nucleus via stress fibers and other mechanotransducing proteins. YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are the main transcriptional effector molecules of the hippo signaling pathway which are the key mechanosensory and mechanotransducers of the mechanical cues. It has been observed that on softer substrates the cells spread less, apply less traction, and the chromatin remains more condensed.

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    1. Kureel, S.K., Mogha, P., Khadpekar, A., Kumar, V., Joshi, R., Das, S., Bellare, J. and Majumder, A., 2019. Soft substrate maintains proliferative and adipogenic differentiation potential of human mesenchymal stem cells on long-term expansion by delaying senescence. Biology open, 8(4), p.bio039453.

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    2.  Mogha, P., Iyer, S. and Majumder, A., 2023. Extracellular matrix protein gelatin provides higher expansion, reduces size heterogeneity, and maintains cell stiffness in a long-term culture of mesenchymal stem cells. Tissue and Cell, 80, p.101969.

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The interplay between substrate rigity and chromatin condensation in controlling cell behaviour such as replicative and oxidative stress mediated ageing, DNA damage, and more​

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​Maintaining hMSC health and potency during long-term expansion has been a significant challenge in the field. MLab investigates the complex relationship between mechanical forces, chromatin organization, and cellular senescence in hMSCs. We've discovered that specific mechanical conditions can delay cellular senescence by influencing chromatin condensation. We also found that condensing the chromatin delays replicative senescence of hMSCs by protecting the chromatin from DNA damage. Also, the effect of substrate rigidity can be overriden by application of chromatin modifiers to the cells.

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    1. Joshi, R., Suryawanshi, T., Mukherjee, S., Shukla, S., & Majumder, A. (2024). Chromatin Condensation Delays Senescence in Human Mesenchymal Stem Cells by Safeguarding Nuclear Damages during In Vitro Expansion. Journal of Tissue Engineering and Regenerative Medicine, 2024(1), 1543849.

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    2. Joshi, R., Muralidharan, P.D., Yadav, P., Dharnidharka, V. and Majumder, A., 2022. Histone deacetylase inhibitor overrides the effect of soft hydrogel on the mechanoresponse of human mesenchymal stem cells. BioRxiv, pp.2022-01.​

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Effect of substrate viscoelasticity on cellular migration​

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​By developing tunable viscoelastic materials that mimic the complex mechanical environments found in living tissues using polyacrylamide gels, we investigate how cells sense and respond to these properties.

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    1. Shirke, P.U., Goswami, H., Kumar, V., Shah, D., Beri, S., Das, S., Bellare, J., Mayor, S., Venkatesh, K.V., Seth, J.R. and Majumder, A., 2021. “Viscotaxis”-directed migration of mesenchymal stem cells in response to loss modulus gradient. Acta biomaterialia, 135, pp.356-367.

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The role of substrate stiffness in controlling glioblastoma aggressiveness

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MLab also focuses on the aspect of mechanobiology in Glioblastoma Multiforme (GBM), an aggressive brain cancer known for its resistance to current therapies. We investigate how mechanical signals in the tumor microenvironment influence GBM cell behavior. We observed that recurrent GBM cells exhibit increased proliferation, invasion, migration, and resistance to EGFR inhibitors compared to parent cells. Also the recurrent cells cultured on soft substrates (0.5 kPa) show higher in vivo tumorigenicity and recurrence than parent cells, a difference not observed in traditional plastic culture conditions. This highlights the importance of mimicking the mechanical microenvironment in studying GBM. Our work has also identified PLEKHA7 as a potential novel target for recurrent GBM treatment.

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    1. Acharekar, A., Bachal, K., Shirke, P., Thorat, R., Banerjee, A., Gardi, N., Majumder, A. and Dutt, S., 2023. Substrate stiffness regulates the recurrent glioblastoma cell morphology and aggressiveness. Matrix Biology, 115, pp.107-127.

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Effect of substrate topography on cell behaviour

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Cellular alignment is important for the proper functioning of different tissues such as muscles or blood vessel walls. It has been shown that micro-and nanoscale anisotropic topological features on cell culture substrates can control cellular orientation. We reported that a replica of the groove-like anisotropic patterns of the abaxial side of a Dracaena sanderiana (bamboo) leaf can be used for large-area patterning of cells. Further, we observed enhanced neuronal differentiation of SHSY5Y cells on biomimicked pattern compared to flat PDMS. We also observed that changes in the topography pattern such as concave and convex structures govern cellular morphology, adhesion and proliferation. 

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    1. Yadav, S., Joshi, R. and Majumder, A., 2024. Concave/Convex Curvature of Anisotropic Grooves Differentially Alters Cellular Morphology, Adhesion, and Proliferation. Langmuir.

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    2. Yadav, S. and Majumder, A., 2022. Biomimicked large-area anisotropic grooves from Dracaena sanderiana leaf enhances cellular alignment and subsequent differentiation. Bioinspiration & Biomimetics, 17(5), p.056002.

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Understanding the anti-diabetic effect of phytochemicals in tissue relevant diabetic models

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Investigating the role of substrate stiffness and phytochemicals in diabetic microenvironments to provide crucial insights into how mechanical cues and natural compounds influence cellular behavior and wound-healing processes in diabetes.

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The interplay betwen long-non coding RNAs and tissue specific rigidity in the context of cancer and tumorigenesis

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Understanding the role of mechanosensing long non-coding RNAs (lncRNAs) in cancer progression and chemoresistance, with a primary focus on Glioblastoma Multiforme (GBM). We employ a multidisciplinary approach, combining computational methods with molecular and cell biology techniques to unravel the complex interplay between mechanical cues and lncRNA function. Our study examines how substrate stiffness in both 2D and 3D model systems affects lncRNA expression and subsequent cancer cell behavior.