Manish Ayushman

All Publications

• Dynamically Crosslinked PEG Hydrogels Reveal a Critical Role of Viscoelasticity in Modulating Glioblastoma Fates and Drug Responses in 3D. Advanced healthcare materials Sinha, S., Ayushman, M., Tong, X., Yang, F. 2022: e2202147

  Abstract

  Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor in adults. Hydrogels have been employed as 3D in-vitro culture models to elucidate how matrix cues such as stiffness and degradation drive GBM progression and drug responses. Recently, viscoelasticity has been identified as an important niche cue in regulating stem cell differentiation and morphogenesis in 3D. Brain is a viscoelastic tissue, yet how viscoelasticity modulates GBM fate and drug response remains largely unknown. Using dynamic hydrazone crosslinking chemistry, we report a poly(ethylene-glycol) (PEG)-based hydrogel system with brain-mimicking stiffness and tunable stress relaxation to interrogate the role of viscoelasticity on GBM fates in 3D. The hydrogel design allows tuning stress relaxation without changing stiffness, biochemical ligand density, or diffusion. Our results reveal that increasing stress relaxation promotes invasive GBM behavior, such as cell spreading, migration, and GBM stem-like cell (GSC) marker expression. Furthermore, increasing stress relaxation enhances GBM proliferation and drug sensitivity. Stress-relaxation induced changes on GBM fates and drug response were found to be mediated through the cytoskeleton andtransient receptor potential vanilloid-type 4 (TRPV4). These results highlight the importance of incorporating viscoelasticity into 3D in-vitro GBM models and provide novel insights into how viscoelasticity modulates GBM cell fates. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/adhm.202202147

  View details for PubMedID 36239185

• Sliding hydrogels enhance MSC chondrogenesis by facilitating early stage cytoskeletal/nuclear dynamics and mechanical loading Ayushman, M., Tong, X., Yang, F. CELL PRESS. 2022: 265A

  View details for Web of Science ID 000759523001552

• Interfacial energy driven distinctive pattern formation during the drying of blood droplets. Journal of colloid and interface science Mukhopadhyay, M., Ray, R., Ayushman, M., Sood, P., Bhattacharyya, M., Sarkar, D., DasGupta, S. 2020; 573: 307-316

  Abstract

  Dried blood droplet morphology may potentially serve as an alternative biomarker for several patho-physiological conditions. The deviant properties of the red blood cells and the abnormal composition of diseased samples are hypothesized to manifest through unique cell-cell and cell-substrate interactions leading to different morphological patterns. Identifying distinctive morphological trait from a large sample size and proposing confirmatory explanations are necessary to establish the signatory pattern as a potential biomarker to differentiate healthy and diseased samples.Comprehensive experimental investigation was undertaken to identify the signatory dried blood droplet patterns. The corresponding image based analysis was in turn used to differentiate the blood samples with a specific haematological disorder "Thalassaemia" from healthy ones. Relevant theoretical analysis explored the role of cell-surface and cell-cell interactions pertinent to the formation of the distinct dried patterns.The differences observed in the dried blood patterns, specifically the radial crack lengths, were found to eventuate from the differences in the overall interaction energies of the system. A first-generation theoretical analysis, with the mean field approximation, also confirmed similar outcome and justified the role of the different physico-chemical properties of red blood cells in diseased samples resulting in shorter radial cracks.

  View details for DOI 10.1016/j.jcis.2020.04.008

  View details for PubMedID 32289626

• DCTN5 mutant mice reveal a role for dynactin in lens biogenesis Yeh, T., Zion, E., Caverts, A., Ayushman, M., Dong, F., Zhao, H., Schroer, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800705227

• Analysis of the Distinct Pattern Formation of Globular Proteins in the Presence of Micro- and Nanoparticles. The journal of physical chemistry. B Sett, A., Ayushman, M., Dasgupta, S., DasGupta, S. 2018; 122 (38): 8972-8984

  Abstract

  Pattern formation during evaporation of biofluids has numerous biomedical applications, e.g., in disease identification. The drying of a bidisperse colloidal droplet involves formation of coffee ring patterns owing to the deposition of constituent particles. In the present study, we examine the distinctly different pattern formations during the drying of a colloidal solution depending on the nature of the constituent proteins. The pattern formations of two oppositely charged proteins, namely HSA and lysozyme, have been studied in the presence of fluorescence polystyrene beads of two different sizes (providing better image contrast for further analysis). The variation of pattern formation has been studied by varying the concentrations of the proteins as well as the particles. Furthermore, using image analysis, the patterns are segmented into different regions for quantification. To explain the variations in the patterns, we delve into the interplay of the interactions, especially the capillary and the DLVO forces (between the particles and the substrate). The developed methodology based on the coffee ring effect may be used to identify individual proteins.

  View details for DOI 10.1021/acs.jpcb.8b05325

  View details for PubMedID 30185036