Publications by authors named "Saraswathibhatla A"
Article Synopsis
- A study using single-cell RNA sequencing analyzed ductal carcinoma in situ (DCIS) to understand its growth mechanisms and how it may progress to invasive cancer.
- Researchers identified a mix of cancerous and normal epithelial cells, uncovering significant genetic diversity and different cell states driven by estrogen receptor expression.
- The findings suggest that changes in specific cell states and loss of basement membrane integrity are linked to the transition from DCIS to invasive breast cancer, highlighting the biological complexity of preinvasive breast diseases.
Article Synopsis
- Breast cancer becomes invasive when carcinoma cells break through the basement membrane (BM), a barrier that separates the tumor from surrounding tissue.
- Researchers created a 3D model to study how multiple cancer cells invade the BM collectively, finding that they use a combination of proteases and mechanical forces without relying on invadopodia.
- The study reveals that the invasion process involves both the expansion of cell volume, which stretches the BM, and local forces that help breach it, highlighting a key mechanism in cancer metastasis.
Article Synopsis
- Circulating monocytes can differentiate into macrophages in tumors and need to migrate through a dense collagen-rich environment to do so.
- Research shows that increased stiffness and faster stress relaxation of the surrounding matrix enhance monocyte migration.
- Monocyte migration relies on actin polymerization at the leading edge rather than matrix adhesions, allowing them to create paths through the viscous matrices.
Mechanical properties of extracellular matrices (ECMs) regulate essential cell behaviours, including differentiation, migration and proliferation, through mechanotransduction. Studies of cell-ECM mechanotransduction have largely focused on cells cultured in 2D, on top of elastic substrates with a range of stiffnesses. However, cells often interact with ECMs in vivo in a 3D context, and cell-ECM interactions and mechanisms of mechanotransduction in 3D can differ from those in 2D.
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- In early breast cancer progression, cancer cells invade the basement membrane as a crucial step toward metastasis, relying on proteases and physical forces for this process.
- A new method was developed to measure the forces exerted by breast cancer cells during their invasion in a 3D culture environment, highlighting the use of multiple-particle tracking and magnetic microrheometry.
- The study found that cancer cell protrusions generate forces ranging from picoNewtons to nanoNewtons, with stepwise force increases occurring every 30 seconds to 6 minutes during the invasion process.
During tissue development and repair, cells contract and expand in coordination with their neighbors, giving rise to tissue deformations that occur on length scales far larger than that of a single cell. The biophysical mechanisms by which the contractile forces of each cell cause deformations on multicellular length scales are not fully clear. To investigate this question, we began with the principle of force equilibrium, which dictates a balance of tensile forces between neighboring cells.
View Article and Find Full Text PDFIn collective cell migration, the motion results from forces produced by each cell and transmitted to the neighboring cells and to the substrate. Because inertia is negligible and the migration occurs over long time scales, the cell layer exhibits viscous behavior, where force and motion are connected by an apparent friction that results from the breaking and forming of adhesive bonds at the cell-cell and cell-substrate interfaces. Most theoretical models for collective migration include an apparent friction to connect force and motion, with many models making predictions that depend on the ratio of cell-cell and cell-substrate friction.
View Article and Find Full Text PDFCells move in collective groups in biological processes such as wound healing, morphogenesis, and cancer metastasis. How active cell forces produce the motion in collective cell migration is still unclear. Many theoretical models have been introduced to elucidate the relationship between the cell's active forces and different observations about the collective motion such as collective swirls, oscillations, and rearrangements.
View Article and Find Full Text PDFWell-controlled 2D cell culture systems advance basic investigations in cell biology and provide innovative platforms for drug development, toxicity testing, and diagnostic assays. These cell culture systems have become more advanced in order to provide and to quantify the appropriate biomechanical and biochemical cues that mimic the milieu of conditions present . Here we present an innovative 2D cell culture system to investigate human stem cell-derived cardiomyocytes, the muscle cells of the heart responsible for pumping blood throughout the body.
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