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Syncytial cells contain multiple nuclei and have local distribution and function of cellular components despite being synthesized in a common cytoplasm. The syncytial Drosophila blastoderm embryo shows reduced spread of organelle and plasma membrane-associated proteins between adjacent nucleo-cytoplasmic domains. Anchoring to the cytoarchitecture within a nucleo-cytoplasmic domain is likely to decrease the spread of molecules; however, its role in restricting this spread has not been assessed. In order to analyze the cellular mechanisms that regulate the rate of spread of plasma membrane-associated molecules in the syncytial Drosophila embryos, we express a pleckstrin homology (PH) domain in a localized manner at the anterior of the embryo by tagging it with the bicoid mRNA localization signal.

Cardiac myosin-binding protein C (cMyBP-C) modulates cardiac contractility through putative interactions with the myosin S2 tail and/or the thin filament. The relative contribution of these binding-partner interactions to cMyBP-C modulatory function remains unclear. Hence, we developed a “nanosurfer” assay as a model system to interrogate these cMyBP-C binding-partner interactions. Synthetic thick filaments were generated using recombinant human β-cardiac myosin subfragments (HMM or S1) attached to DNA nanotubes, with 14 or 28 nm spacing, corresponding to the 14.3 nm myosin spacing in native thick filaments.

Contrasting most known bacterial motility mechanisms, a bacterial sliding motility discovered in at least two Gram-positive bacterial families does not depend on designated motors. Instead, the cells maintain end-to-end connections following cell divisions to form long chains and exploit cell growth and division to push the cells forward. To investigate the dynamics of this motility mechanism, we constructed a mechanical model that depicts the interplay of the forces acting on and between the cells comprising the chain.

Cancer starts after initially healthy tissue cells accumulate several specific mutations or other genetic alterations. The dynamics of tumor formation is a very complex phenomenon due to multiple involved biochemical and biophysical processes. It leads to a very large number of possible pathways on the road to final fixation of all mutations that marks the beginning of the cancer, complicating the understanding of microscopic mechanisms of tumor formation. We present a new theoretical framework of analyzing the cancer initiation dynamics by exploring the properties of effective free-energy landscape of the process.

The filament of a bacterial flagellum is a tube-like organelle made of single protein – flagellin, and assembled into multiple polymorphic forms. The filament can be further discretized into four subunit domains (D0, D1, D2 and D3) along the radial direction. However, it remains unclear which subunit domain plays an important role in regulating the rigidity of the filament. In this article, we address how the absence of two outer subunit domains (D2 and D3) affects the bending stiffness of the bacterium B.

Glioblastoma multiforme (GBM) is the most aggressive and prevalent form of brain cancer, with an expected survival of 12-15 months following diagnosis. GBM affects the glial cells of the central nervous system, which impairs regular brain function including memory, hearing, and vision. GBM has virtually no long-term survival even with treatment, requiring novel strategies to understand disease progression. Here, we identified a somatic mutation in OR2T7, a G-protein coupled receptor (GPCR), that correlates with reduced progression free survival for glioblastoma (log rank p-value = 0.05), suggesting a possible role in tumor progression.

Amyloid-beta (Aβ) and islet amyloid polypeptide (IAPP) are small peptides, classified as amyloids, that have the potential to self-assemble and form cytotoxic species, such as small soluble oligomers and large insoluble fibrils. The formation of Aβ aggregates facilitates the progression of Alzheimer’s disease (AD), while IAPP aggregates induce pancreatic β-cell apoptosis, leading to exacerbation of Type 2 diabetes (T2D). Cross-amyloid interactions between Aβ and IAPP have been described both in vivo and in vitro, implying the role of Aβ or IAPP as modulators of cytotoxic self-aggregation of each species, and suggesting that Aβ-IAPP interactions are a potential molecular link between AD and T2D.

Allosteric regulation is essential to control biological function. In addition, allosteric sites offer a promising venue for selective drug targeting. However, accurate mapping of allosteric sites remains challenging since allostery relies on often subtle, yet functionally relevant, structural and dynamical changes. A viable approach proposed to overcome such challenge is the chemical shift covariance analysis (CHESCA). Although CHESCA offers an exhaustive map of allosteric networks, it is critical to define the core allosteric sites to be prioritized in subsequent functional studies or the design of allosteric drugs.

Biomolecular thermodynamics, particularly for DNA, are frequently determined via van’t Hoff analysis of optically-measured melt curves. Accurate and precise values of thermodynamic parameters are essential for the modelling of complex systems involving cooperative effects, such as RNA tertiary structure and DNA origami because the uncertainties associated with each motif in a folding energy landscape can compound, significantly reducing the power of predictive models. We follow the sources of uncertainty as they propagate through a typical van’t Hoff analysis to derive best practices for melt experiments and subsequent data analysis, assuming perfect signal baseline correction.

Interactions between ions and water at hydrophobic interfaces within ion channels and nanopores are suggested to play a key role in the movement of ions across biological membranes. Previous molecular dynamics (MD) simulations have shown that anion affinity for aqueous/hydrophobic interfaces can be markedly influenced by including polarization effects through an electronic continuum correction (ECC). Here, we designed a model biomimetic nanopore to imitate the polar pore openings and hydrophobic gating regions found in pentameric ligand-gated ion channels.

Single-molecule enzymology (SME) methods have enabled the observation of heterogeneous catalytic activities within a single enzyme population. Heterogenous activity is hypothesized to originate from conformational changes in the enzyme that result from changes in the local environment leading to catalytically-active substates. Here, we use SME to investigate the mechanisms of heterogenous activity exhibited by tissue nonspecific alkaline phosphatase (TNSALP), which reveals two subpopulations with different catalytic activities.

In embryogenesis and cancer invasion, cells collectively migrate as a cluster in 3D tissues. Many studies have elucidated mechanisms of either individual or collective cell migration on 2D substrates; however, it remains unclear how cells collectively migrate as a cluster through 3D tissues. To address this issue, we considered the interfacial tension at cell-cell boundaries expressing cortical actomyosin contractions and cell-cell adhesive interactions. The strength of this tension is polarized; i.e., spatially biased within each cell according to a chemoattractant gradient.