bims-ecemfi 2025-02-02 papers

bioRxiv. 2025 Jan 14. pii: 2025.01.11.632563. [Epub ahead of print]

Tissue-dependent mechanosensing by cells derived from human tumors.

Kshitiz Parihar, Jonathan Nukpezah, Daniel V Iwamoto, Katrina Cruz, Fitzroy J Byfield, LiKang Chin, Maria E Murray, Melissa G Mendez, Anne S van Oosten, Anne Herrmann, Elisabeth E Charrier, Peter A Galie, Megan Donlick, Tongkeun Lee, Paul A Janmey, Ravi Radhakrishnan.

Alterations of the extracellular matrix (ECM), including both mechanical (such as stiffening of the ECM) and chemical (such as variation of adhesion proteins and deposition of hyaluronic acid (HA)) changes, in malignant tissues have been shown to mediate tumor progression. To survey how cells from different tissue types respond to various changes in ECM mechanics and composition, we measured physical characteristics (adherent area, shape, cell stiffness, and cell speed) of 25 cancer and 5 non-tumorigenic cell lines on 7 different substrate conditions. Our results indicate substantial heterogeneity in how cell mechanics changes within and across tissue types in response to mechanosensitive and chemosensitive changes in ECM. The analysis also underscores the role of HA in ECM with some cell lines showing changes in cell mechanics in response to presence of HA in soft substrate that are similar to those observed on stiff substrate. This pan-cancer investigation also highlights the importance of tissue-type and cell line specificity for inferences made based on comparison between physical properties of cancer and normal cells. Lastly, using unsupervised machine learning, we identify phenotypic classes that characterize the physical plasticity, i.e. the distribution of physical feature values attainable, of a particular cell type in response to different ECM-based conditions.

DOI: https://doi.org/10.1101/2025.01.11.632563

Matrix Biol Plus. 2025 Feb;25 100167

Dynamically changing extracellular matrix stiffness drives Schwann cell phenotype.

Alyssa Montgomery, Jennifer Westphal, Andrew E Bryan, Greg M Harris.

Schwann cells (SCs) hold key roles in axonal function and maintenance in the peripheral nervous system (PNS) and are a critical component to the regeneration process following trauma. Following PNS trauma, SCs respond to both physical and chemical signals to modify phenotype and assist in the regeneration of damaged axons and extracellular matrix (ECM). There is currently a lack of knowledge regarding the SC response to dynamic, temporal changes in the ECM brought on by swelling and the development of scar tissue as part of the body's wound-healing process. Thus, this work seeks to utilize a biocompatible, mechanically tunable biomaterial to mimic changes in the microenvironment following injury and over time. Previously, we have reported that ECM cues such as ligand type and substrate stiffness impact SC phenotype and plasticity, which was demonstrated by SCs on mechanically stable biomaterials. However, to better realize SC potential for plasticity following traumatic injury, a UV-tunable polydimethylsiloxane (PDMS) substrate with dynamically changing stiffness was utilized to mimic changes over time in the microenvironment. The dynamic biomaterial showed an increase in stress fibers, greater YAP expression, and fluctuations in c-Jun production in SCs in comparison to stiff and soft static controls. Utilizing biomaterials to better understand the role between temporal mechanical dynamics and SC phenotype holds a very high potential for developing future PNS therapies.

Keywords: Biomaterials; Extracellular matrix; Fibrosis; Mechanotransduction; PNS injury; Schwann cell

DOI: https://doi.org/10.1016/j.mbplus.2024.100167

Nano Lett. 2025 Jan 30.

Nanoscale Ligand Spacing Regulates Mechanical Force-Induced Cancer Cell Killing.

S Manasa Veena, Dixiao Chen, Akshay Kumar, Rudra Pratap, Jennifer L Young, Ajay Tijore.

Cancer cells sense and respond to the extracellular environment, with differences in nanoscale ligand spacing affecting their behavior. Emerging reports show that stretch/ultrasound-mediated mechanical forces promote apoptosis (mechanoptosis) by increasing myosin contractility. Since myosin contractility is critical for nanoscale-ligand spacing-regulated cell behavior, we study the effect of ligand spacing on mechanoptosis. Gold nanoparticle arrays were created with 35, 50, and 70 nm spacings and functionalized with cyclic-RGD peptide. Interestingly, the highest level of apoptosis was observed on 50 and 70 nm ligand spacing, where increased myosin contractility and peripheral Piezo1 channel localization causing calcium influx were observed. Perturbing cell-matrix interactions by nanomolar doses of Cilengitide (cyclic RGD pentapeptide) increases mechanoptosis on 35 nm ligand spacing to similar levels observed on 50 and 70 nm. Thus, nanoscale-level changes in binding domains regulate mechanoptosis through cell-matrix mediated mechanotransduction, and the synergistic action of ultrasound and Cilengitide can ultimately be applied to enhance tumor treatment.

Keywords: Piezo1; apoptosis; mechanical forces; mechanotransduction; nanospacing; ultrasound

DOI: https://doi.org/10.1021/acs.nanolett.4c05858