Clays have been used as early as 2500 BC in the human civilization for numerous biomedical applications. Ease of availability, biocompatibility and versatility of these unique charged 2D structures abundantly...

Actin molecules are essential structural components of the cellular cytoskeleton. Here, we report a comprehensive analysis of F-actin’s deformation behavior and highlight underlying mechanisms using steered molecular dynamics simulations (SMD). The investigation of F-actin was done under tension, compression, bending, and torsion. We report that the dissociation pattern of conformational locks at intrastrand and interstrand G-actin interfaces regulates the deformation response of F-actin. The conformational locks at the G-actin interfaces are portrayed by a spheroidal joint, interlocking serrated plates’ analogy. Further, the SMD simulation approach was utilized to evaluate Young’s modulus, flexural rigidity, persistent length, and torsional rigidity of F-actin, and the values obtained were found to be consistent with available experimental data. The evaluation of the mechanical properties of actin and the insight into the fundamental mechanisms contributing to its resilience described here are necessary for developing accurate models of eukaryotic cells and for assessing cellular viability and mobility.

Prostate cancer bone metastasis is the leading cause of cancer-related mortality in men in the United States, causing severe damage to skeletal tissue. The treatment of advanced-stage prostate cancer is always challenging due to limited drug treatment options, resulting in low survival rates. There is a scarcity of knowledge regarding the mechanisms associated with the effects of biomechanical cues by interstitial fluid flow on prostate cancer cell growth and migration. We have designed a novel bioreactor system to demonstrate the impact of interstitial fluid flow on the migration of prostate cancer cells to the bone during extravasation. First, we demonstrated that a high flow rate induces apoptosis in PC3 cells via TGF-β1 mediated signaling; thus, physiological flow rate conditions are optimum for cell growth. Next, to understand the role of interstitial fluid flow in prostate cancer migration, we evaluated the migration rate of cells under static and dynamic conditions in the presence or absence of bone. We report that CXCR4 levels were not significantly changed under static and dynamic conditions, indicating that CXCR4 activation in PC3 cells is not influenced by flow conditions but by the bone, where CXCR4 levels were upregulated. The bone-upregulated CXCR4 levels led to increased MMP-9 levels resulting in a high migration rate in the presence of bone. In addition, upregulated levels of αvβ3 integrins under fluid flow conditions, contributed to an overall increase in the migration rate of PC3 cells. Overall, this study demonstrates the potential role of interstitial fluid flow in prostate cancer invasion. Understanding the critical role of interstitial fluid flow in promoting prostate cancer cell progression will aid in enhancing current therapies for advanced-stage prostate cancer and provide improved treatment options for patients.

Three-dimensional cellular constructs derived from pluripotent stem cells allow the ex vivo study of neurodevelopment and neurological disease within a spatially organized model. However, the robustness and utility of three-dimensional models is impacted by tissue self-organization, size limitations, nutrient supply, and heterogeneity. In this work, we have utilized the principles of nanoarchitectonics to create a multifunctional polymer/bioceramic composite microsphere system for stem cell culture and differentiation in a chemically defined microenvironment. Microspheres could be customized to produce three-dimensional structures of defined size (ranging from >100 to <350 μm) with lower mechanical properties compared with a thin film. Furthermore, the microspheres softened in solution, approaching more tissue-like mechanical properties over time. With neural stem cells (NSCs) derived from human induced pluripotent stem cells, microsphere-cultured NSCs were able to utilize multiple substrates to promote cell adhesion and proliferation. Prolonged culture of NSC-bound microspheres under differentiating conditions allowed the formation of both neural and glial cell types from control and patient-derived stem cell models. Human NSCs and differentiated neurons could also be cocultured with astrocytes and human umbilical vein endothelial cells, demonstrating application for tissue-engineered modeling of development and human disease. We further demonstrated that microspheres allow the loading and sustained release of multiple recombinant proteins to support cellular maintenance and differentiation. While previous work has principally utilized self-organizing models or protein-rich hydrogels for neural culture, the three-dimensional matrix developed here through nanoarchitectonics represents a chemically defined and robust alternative for the in vitro study of neurodevelopment and nervous system disorders.

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