Cellular and Nuclear Forces: An Overview.

Biological cells sample their surrounding microenvironments using nanoscale force sensors on the cell surfaces. These surface-based force and stress sensors generate physical and chemical responses inside the cell. The inherently well-connected cytoskeleton and its physical contacts with the force elements on the nuclear membrane lead these physicochemical responses to cascade all the way inside the cell nucleus, physically altering the nuclear state.

Exploring the role of macromolecular crowding and TNFR1 in cell volume control.

The excessive cosolute densities in the intracellular fluid create a physicochemical condition called macromolecular crowding (MMC). Intracellular MMC entropically maintains the biochemical thermodynamic equilibria by favoring associative reactions while hindering transport processes. Rapid cell volume shrinkage during extracellular hypertonicity elevates the MMC and disrupts the equilibria, potentially ushering cell death.

The Plasma Membrane and Mechanoregulation in Cells.

Cells inhabit a mechanical microenvironment that they continuously sense and adapt to. The plasma membrane (PM), serving as the boundary of the cell, plays a pivotal role in this process of adaptation. In this Review, we begin by examining well-studied processes where mechanoregulation proves significant.

Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells.

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established.

Mechano-regulation by clathrin pit-formation and passive cholesterol-dependent tubules during de-adhesion.

Adherent cells ensure membrane homeostasis during de-adhesion by various mechanisms, including endocytosis. Although mechano-chemical feedbacks involved in this process have been studied, the step-by-step build-up and resolution of the mechanical changes by endocytosis are poorly understood. To investigate this, we studied the de-adhesion of HeLa cells using a combination of interference reflection microscopy, optical trapping and fluorescence experiments.

Connexin 43 mediated collective cell migration is independent of Golgi orientation.

Cell migration is vital for multiple physiological functions and is involved in the metastatic dissemination of tumour cells in various cancers. For effective directional migration, cells often reorient their Golgi apparatus and, therefore, the secretory traffic towards the leading edge. However, not much is understood about the regulation of Golgi's reorientation.

Use of a multi-method approach to rapidly assess the impact of public health policies at the state and local level: a case study of flavored e-cigarette policies.

Background: E-cigarettes are the most-commonly used tobacco product by youth since 2014. To prevent youth access and use of e-cigarettes, many U.S.

Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts.

Here, we study the time-dependent regulation of fluctuation-tension during myogenesis and the role of the fusogen, myomerger. We measure nanometric height fluctuations of the basal membrane of C2C12 cells after triggering differentiation. Fusion of cells increases fluctuation-tension but prefers a transient lowering of tension (at ~2-24 h).

Student tobacco use, secondhand smoke exposure, and policy beliefs before and after implementation of a tobacco-free campus policy: Analysis of five U.S. college and university campuses.

The adoption of comprehensive tobacco policies by colleges and universities may help reduce student tobacco use. To this end, The American Cancer Society's Tobacco-Free Generation Campus Initiative (TFGCI) awarded grants to 106 higher learning institutions to adopt 100% tobacco-free campus policies. This study measured changes in student tobacco use, reported exposure to secondhand smoke, and support for types of tobacco policies among five TFGCI grantee institutions who implemented 100% tobacco-free policies.

Two Consecutive Prolines in the Fusion Peptide of Murine β-Coronavirus Spike Protein Predominantly Determine Fusogenicity and May Be Essential but Not Sufficient to Cause Demyelination.

Combined in silico, in vitro, and in vivo comparative studies between isogenic-recombinant Mouse-Hepatitis-Virus-RSA59 and its proline deletion mutant, revealed a remarkable contribution of centrally located two consecutive prolines (PP) from Spike protein fusion peptide (FP) in enhancing virus fusogenic and hepato-neuropathogenic potential. To deepen our understanding of the underlying factors, we extend our studies to a non-fusogenic parental virus strain RSMHV2 (P) with a single proline in the FP and its proline inserted mutant, RSMHV2 (PP). Comparative in vitro and in vivo studies between virus strains RSA59(PP), RSMHV2 (P), and RSMHV2 (PP) in the FP demonstrate that the insertion of one proline significantly resulted in enhancing the virus fusogenicity, spread, and consecutive neuropathogenesis.

Effect of heterogeneous substrate adhesivity of follower cells on speed and tension profile of leader cells in primary keratocyte collective cell migration.

In single keratocyte motility, membrane tension is reported to be high at cell-fronts and believed to establish front coherence. To understand role of membrane mechanics in collective cell migration, we study membrane height fluctuations in cell sheets from fish scales using interference reflection microscopy (IRM). We report the monolayer to have cells lacking substrate adhesion and show that such 'non-sticky' cells can form bridges between leader cells and far-away follower cells.

Lessons learned about post-secondary institution tobacco policy change by Tobacco-Free Generation Campus Initiative Grantees, 2018-2020.

Objective: The Tobacco-Free Generation Campus Initiative (TFGCI) granted funding to U.S. post-secondary institutions to assist with creating 100% smoke- and tobacco-free campus policies to prevent young adult tobacco use.

Cell spread area and traction forces determine myosin-II-based cortex thickness regulation.

Actomyosin network under the plasma membrane of cells forms a cortical layer that regulates cellular deformations during different processes. What regulates the cortex? Characterized by its thickness, it is believed to be regulated by actin dynamics, filament-length regulators and myosin motor proteins. However, its regulation by cellular morphology (e.

Smoke-free and tobacco-free colleges and universities in the United States.

Objective: To describe the number and proportion of accredited, degree-granting institutions with 100% smoke-free and 100% tobacco-free protections across the USA and by state.

Methods: Data on postsecondary education institutions from the US Department of Education National Center for Education Statistics Integrated Postsecondary Education Data System 2015, and smoke-free and tobacco-free campus protections from the American Nonsmokers' Rights Foundation's Smokefree and Tobacco-Free Colleges and Universities List 2017, were integrated to calculate the number and proportion of: (1) smoke-free and tobacco-free accredited, degree-granting institutions and (2) students and staff protected by campus policies and state laws. Campus protections are given a 100% smoke-free designation if smoking is not allowed on campus anywhere, at any time; 100% tobacco-free designations extend smoke-free protections to include non-combustible products such as smokeless tobacco.

Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells.

Caveolin-3 is the major structural protein of caveolae in muscle. Mutations in the CAV3 gene cause different types of myopathies with altered membrane integrity and repair, expression of muscle proteins, and regulation of signaling pathways. We show here that myotubes from patients bearing the CAV3 P28L and R26Q mutations present a dramatic decrease of caveolae at the plasma membrane, resulting in abnormal response to mechanical stress.

Cholesterol Depletion by MβCD Enhances Cell Membrane Tension and Its Variations-Reducing Integrity.

Cholesterol depletion by methyl-β-cyclodextrin (MβCD) remodels the plasma membrane's mechanics in cells and its interactions with the underlying cytoskeleton, whereas in red blood cells, it is also known to cause lysis. Currently it's unclear if MβCD alters membrane tension or only enhances membrane-cytoskeleton interactions-and how this relates to cell lysis. We map membrane height fluctuations in single cells and observe that MβCD reduces temporal fluctuations robustly but flattens spatial membrane undulations only slightly.

Cellular and Nuclear Forces: An Overview.

Biological cells sample their surrounding microenvironments using nanoscale force sensors on the cell surfaces. These surface-based force and stress sensors generate physical and chemical responses inside the cell. The inherently well-connected cytoskeleton and its physical contacts with the force elements on the nuclear membrane lead these physicochemical responses to cascade all the way inside the cell nucleus, physically altering the nuclear state.

Mapping Cell Membrane Fluctuations Reveals Their Active Regulation and Transient Heterogeneities.

Shape fluctuations of the plasma membrane occur in all cells, are incessant, and are proposed to affect membrane functioning. Although studies show how membrane fluctuations are affected by cellular activity in adherent cells, their spatial regulation and the corresponding change in membrane mechanics remain unclear. In this article, we study how ATP-driven activities and actomyosin cytoskeleton impact basal membrane fluctuations in adherent cells.

"Love Your Love Life": Disadvantaged African American Adolescents Cocreate Psychoeducational Romantic and Sexual Health Resources.

Sexually transmitted disease transmission, dating violence, trafficking, and unplanned pregnancy disproportionately afflict disadvantaged African American adolescents, and social services to effectively remedy this crisis need improvement. Moreover, disadvantaged African American adolescents have been significantly underrepresented in mental health, social services, and best practices research, so existing evidence-based practice models are insufficiently inclusive of these adolescents' perspectives. As a remedy, this study describes a formative evaluation of a youth-led, participatory action-based summer and after-school program, Love Your Love Life.

Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro.

Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids.

Cells respond to mechanical stress by rapid disassembly of caveolae.

The functions of caveolae, the characteristic plasma membrane invaginations, remain debated. Their abundance in cells experiencing mechanical stress led us to investigate their role in membrane-mediated mechanical response. Acute mechanical stress induced by osmotic swelling or by uniaxial stretching results in a rapid disappearance of caveolae, in a reduced caveolin/Cavin1 interaction, and in an increase of free caveolins at the plasma membrane.

Dynamic organization of chromatin assembly and transcription factories in living cells.

The interphase nucleus is an active organelle involved in processing genetic information. In higher order eukaryotes, information control is compartmentalized - for example at the scale of inter-chromosome territories and nuclear bodies. Regulatory proteins, nuclear bodies and chromatin assembly are found to be highly dynamic within the nucleus of primary cells and through cellular differentiation programs.