Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

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Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190628115644 ◽

2019 ◽

Vol 19 (16) ◽

pp. 1464-1483 ◽

Cited By ~ 2

Author(s):

Peng He ◽

Wenbo Zhou ◽

Mingyao Liu ◽

Yihua Chen

Keyword(s):

G Protein ◽

Cell Biology ◽

Immune Cell ◽

G Protein Coupled Receptors ◽

Treatment Modalities ◽

Immune Checkpoints ◽

Considerable Proportion ◽

Prostaglandin E ◽

Recent Advances ◽

G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

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Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽

10.3390/antiox10071002 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1002

Author(s):

Fabiola Marino ◽

Mariangela Scalise ◽

Eleonora Cianflone ◽

Luca Salerno ◽

Donato Cappetta ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cell ◽

Physical Exercise ◽

Cell Biology ◽

Molecular Mechanisms ◽

Heart Function ◽

Stem Cell Biology ◽

Myocardial Repair ◽

Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

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Protein and Polysaccharide-Based Electroactive and Conductive Materials for Biomedical Applications

Molecules ◽

10.3390/molecules26154499 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4499

Author(s):

Xiao Hu ◽

Samuel Ricci ◽

Sebastian Naranjo ◽

Zachary Hill ◽

Peter Gawason

Keyword(s):

Cell Biology ◽

Biomedical Applications ◽

Human Life ◽

Electrically Conductive ◽

Conductive Materials ◽

Production Strategies ◽

Integral Role ◽

Material Sciences ◽

Novel Drug

Electrically responsive biomaterials are an important and emerging technology in the fields of biomedical and material sciences. A great deal of research explores the integral role of electrical conduction in normal and diseased cell biology, and material scientists are focusing an even greater amount of attention on natural and hybrid materials as sources of biomaterials which can mimic the properties of cells. This review establishes a summary of those efforts for the latter group, detailing the current materials, theories, methods, and applications of electrically conductive biomaterials fabricated from protein polymers and polysaccharides. These materials can be used to improve human life through novel drug delivery, tissue regeneration, and biosensing technologies. The immediate goal of this review is to establish fabrication methods for protein and polysaccharide-based materials that are biocompatible and feature modular electrical properties. Ideally, these materials will be inexpensive to make with salable production strategies, in addition to being both renewable and biocompatible.

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Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjab010 ◽

2021 ◽

Author(s):

Jonathon A Ditlev

Keyword(s):

Phase Separation ◽

Cell Biology ◽

Cellular Environment ◽

Condensate Formation ◽

Associated Proteins ◽

Available Technology ◽

And Function ◽

Surrounding Membrane

Abstract Liquid‒liquid phase separation (LLPS) of biomolecules has emerged as an important mechanism that contributes to cellular organization. Phase separated biomolecular condensates, or membrane-less organelles, are compartments composed of specific biomolecules without a surrounding membrane in the nucleus and cytoplasm. LLPS also occurs at membranes, where both lipids and membrane-associated proteins can de-mix to form phase separated compartments. Investigation of these membrane-associated condensates using in vitro biochemical reconstitution and cell biology has provided key insights into the role of phase separation in membrane domain formation and function. However, these studies have generally been limited by available technology to study LLPS on model membranes and the complex cellular environment that regulates condensate formation, composition, and function. Here, I briefly review our current understanding of membrane-associated condensates, establish why LLPS can be advantageous for certain membrane-associated condensates, and offer a perspective for how these condensates may be studied in the future.

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The Role of Mechanical Tension in Neurons

MRS Proceedings ◽

10.1557/proc-1274-qq01-06 ◽

2010 ◽

Vol 1274 ◽

Cited By ~ 1

Author(s):

Taher Saif ◽

Jagannathan Rajagopalan ◽

Alireza Tofangchi

Keyword(s):

Mechanical Response ◽

Mechanical Forces ◽

Active Tension ◽

Mechanical Tension ◽

Deformation Response ◽

Linear Force ◽

Tension Regulation ◽

Over Time

AbstractWe used high resolution micromechanical force sensors to study the in vivo mechanical response of embryonic Drosophila neurons. Our experiments show that Drosophila axons have a rest tension of a few nN and respond to mechanical forces in a manner characteristic of viscoelastic solids. In response to fast externally applied stretch they show a linear force-deformation response and when the applied stretch is held constant the force in the axons relaxes to a steady state value over time. More importantly, when the tension in the axons is suddenly reduced by releasing the external force the neurons actively restore the tension, sometimes close to their resting value. Along with the recent findings of Siechen et al (Proc. Natl. Acad. Sci. USA 106, 12611 (2009)) showing a link between mechanical tension and synaptic plasticity, our observation of active tension regulation in neurons suggest an important role for mechanical forces in the functioning of neurons in vivo.

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