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Nature Communications Aug 2023Photodynamic hydrogel biomaterials have demonstrated great potential for user-triggered therapeutic release, patterned organoid development, and four-dimensional control...
Photodynamic hydrogel biomaterials have demonstrated great potential for user-triggered therapeutic release, patterned organoid development, and four-dimensional control over advanced cell fates in vitro. Current photosensitive materials are constrained by their reliance on high-energy ultraviolet light (<400 nm) that offers poor tissue penetrance and limits access to the broader visible spectrum. Here, we report a family of three photolabile material crosslinkers that respond rapidly and with unique tricolor wavelength-selectivity to low-energy visible light (400-617 nm). We show that when mixed with multifunctional poly(ethylene glycol) macromolecular precursors, ruthenium polypyridyl- and ortho-nitrobenzyl (oNB)-based crosslinkers yield cytocompatible biomaterials that can undergo spatiotemporally patterned, uniform bulk softening, and multiplexed degradation several centimeters deep through complex tissue. We demonstrate that encapsulated living cells within these photoresponsive gels show high viability and can be successfully recovered from the hydrogels following photodegradation. Moving forward, we anticipate that these advanced material platforms will enable new studies in 3D mechanobiology, controlled drug delivery, and next-generation tissue engineering applications.
Topics: Hydrogels; Biocompatible Materials; Biophysics; Drug Delivery Systems; Light
PubMed: 37640707
DOI: 10.1038/s41467-023-40805-w -
Nature Communications Sep 2023HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site...
HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site mutations R132T and T216I rescue infectivity. Capsid lattice stability was studied by solving seven crystal structures (in native background), including P38A, P38A/T216I, E45A, E45A/R132T CA, using molecular dynamics simulations of lattices, cryo-electron microscopy of assemblies, time-resolved imaging of uncoating, biophysical and biochemical characterization of assembly and stability. We report pronounced and subtle, short- and long-range rearrangements: (1) A38 destabilized hexamers by loosening interactions between flanking CA protomers in P38A but not P38A/T216I structures. (2) Two E45A structures showed unexpected stabilizing CA-CA inter-hexamer interactions, variable R18-ring pore sizes, and flipped N-terminal β-hairpin. (3) Altered conformations of E45A α9-helices compared to WT, E45A/R132T, WT, WT, and WT decreased PF74, CPSF6, and Nup153 binding, and was reversed in E45A/R132T. (4) An environmentally sensitive electrostatic repulsion between E45 and D51 affected lattice stability, flexibility, ion and water permeabilities, electrostatics, and recognition of host factors.
Topics: Capsid Proteins; HIV-1; Cryoelectron Microscopy; Capsid; Biophysics
PubMed: 37699872
DOI: 10.1038/s41467-023-41197-7 -
Oncogene Nov 2023Evidence from physical sciences in oncology increasingly suggests that the interplay between the biophysical tumor microenvironment and genetic regulation has... (Review)
Review
Evidence from physical sciences in oncology increasingly suggests that the interplay between the biophysical tumor microenvironment and genetic regulation has significant impact on tumor progression. Especially, tumor cells and the associated stromal cells not only alter their own cytoskeleton and physical properties but also remodel the microenvironment with anomalous physical properties. Together, these altered mechano-omics of tumor tissues and their constituents fundamentally shift the mechanotransduction paradigms in tumorous and stromal cells and activate oncogenic signaling within the neoplastic niche to facilitate tumor progression. However, current findings on tumor biophysics are limited, scattered, and often contradictory in multiple contexts. Systematic understanding of how biophysical cues influence tumor pathophysiology is still lacking. This review discusses recent different schools of findings in tumor biophysics that have arisen from multi-scale mechanobiology and the cutting-edge technologies. These findings range from the molecular and cellular to the whole tissue level and feature functional crosstalk between mechanotransduction and oncogenic signaling. We highlight the potential of these anomalous physical alterations as new therapeutic targets for cancer mechanomedicine. This framework reconciles opposing opinions in the field, proposes new directions for future cancer research, and conceptualizes novel mechanomedicine landscape to overcome the inherent shortcomings of conventional cancer diagnosis and therapies.
Topics: Humans; Mechanotransduction, Cellular; Neoplasms; Signal Transduction; Tumor Microenvironment; Biophysics
PubMed: 37864030
DOI: 10.1038/s41388-023-02844-x -
Journal of Molecular Biology Aug 2023The past decade has seen a revolution in our understanding of how the cellular environment is organized, where an incredible body of work has provided new insights into... (Review)
Review
The past decade has seen a revolution in our understanding of how the cellular environment is organized, where an incredible body of work has provided new insights into the role played by membraneless organelles. These rapid advancements have been made possible by an increasing awareness of the peculiar physical properties that give rise to such bodies and the complex biology that enables their function. Viral infections are not extraneous to this. Indeed, in host cells, viruses can harness existing membraneless compartments or, even, induce the formation of new ones. By hijacking the cellular machinery, these intracellular bodies can assist in the replication, assembly, and packaging of the viral genome as well as in the escape of the cellular immune response. Here, we provide a perspective on the fundamental polymer physics concepts that may help connect and interpret the different observed phenomena, ranging from the condensation of viral genomes to the phase separation of multicomponent solutions. We complement the discussion of the physical basis with a description of biophysical methods that can provide quantitative insights for testing and developing theoretical and computational models.
Topics: Humans; Organelles; Virus Diseases; Biomolecular Condensates; Virus Replication; Viral Genome Packaging; Stress Granules; Genome, Viral; Biopolymers; Phase Transition
PubMed: 36709795
DOI: 10.1016/j.jmb.2023.167988 -
Biochimie Nov 2023Besides the well-known DNA double-helix, non-canonical nucleic acid structures regulate crucial biological activities. Among these oddities, guanine-rich DNA sequences... (Review)
Review
Besides the well-known DNA double-helix, non-canonical nucleic acid structures regulate crucial biological activities. Among these oddities, guanine-rich DNA sequences can form unusual four-stranded secondary structures called G-quadruplexes (G4s). G4-prone sequences have been found in the genomes of most species, and G4s play important roles in essential processes such as transcription, replication, genome integrity and epigenetic regulation. Here, we present a short overview of G-quadruplexes followed by a detailed description of the biophysical and biochemical methods used to characterize G4s in vitro. The principles, experimental details and possible shortcomings of each method are discussed to provide a comprehensive view of the techniques used to study these structures. We aim to provide a set of guidelines for standardizing research on G-quadruplexes; these guidelines are not meant to be a dogmatic set of rules, but should rather provide useful information on the methods currently used to study these fascinating motifs.
Topics: G-Quadruplexes; Epigenesis, Genetic; DNA; Genome
PubMed: 36596406
DOI: 10.1016/j.biochi.2022.12.019 -
FEBS Open Bio Jan 2024Josep Rizo is a Professor of Biophysics, Biochemistry and Pharmacology at the University of Texas Southwestern Medical Center, where he is Virginia Lazenby O'Hara Chair...
Josep Rizo is a Professor of Biophysics, Biochemistry and Pharmacology at the University of Texas Southwestern Medical Center, where he is Virginia Lazenby O'Hara Chair in Biochemistry. He is particularly interested in the study of the mechanisms of neurotransmitter release and intracellular membrane fusion using structural biology, a variety of biophysical techniques and reconstitution approaches. Jose has been a part of the FEBS Open Bio Editorial Board since 2021. In this interview, he shares his insights into developments in the field of neurotransmitter release, describes his move from Spain to the United States, and discusses how sometimes you need to use both logic and scientific hunches.
Topics: United States; Molecular Biology; Neurotransmitter Agents
PubMed: 38050436
DOI: 10.1002/2211-5463.13746 -
Nature Communications Sep 2023To navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a...
To navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a curvature-sensing mechanism underlying obstacle evasion in immune-like cells. Specifically, we propose that actin polymerization at the advancing edge of migrating cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions with inward plasma membrane curvature. The genetic perturbation of this machinery reduces the cells' capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. Our results show how cells can read out their surface topography and utilize actin and plasma membrane biophysics to interpret their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR domain proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.
Topics: Actins; Cell Membrane; Cell Movement; Adaptation, Psychological; Biophysics
PubMed: 37704612
DOI: 10.1038/s41467-023-41173-1 -
Brain Sciences Jul 2023Alzheimer's disease (AD) is a degenerative brain disease, and the condition is difficult to assess. In the past, numerous brain dynamics models have made remarkable... (Review)
Review
Alzheimer's disease (AD) is a degenerative brain disease, and the condition is difficult to assess. In the past, numerous brain dynamics models have made remarkable contributions to neuroscience and the brain from the microcosmic to the macroscopic scale. Recently, large-scale brain dynamics models have been developed based on dual-driven multimodal neuroimaging data and neurodynamics theory. These models bridge the gap between anatomical structure and functional dynamics and have played an important role in assisting the understanding of the brain mechanism. Large-scale brain dynamics have been widely used to explain how macroscale neuroimaging biomarkers emerge from potential neuronal population level disturbances associated with AD. In this review, we describe this emerging approach to studying AD that utilizes a biophysically large-scale brain dynamics model. In particular, we focus on the application of the model to AD and discuss important directions for the future development and analysis of AD models. This will facilitate the development of virtual brain models in the field of AD diagnosis and treatment and add new opportunities for advancing clinical neuroscience.
PubMed: 37626490
DOI: 10.3390/brainsci13081133 -
Cells Aug 2023Optical mapping is a powerful imaging technique widely adopted to measure membrane potential changes and intracellular Ca variations in excitable tissues using... (Review)
Review
Optical mapping is a powerful imaging technique widely adopted to measure membrane potential changes and intracellular Ca variations in excitable tissues using voltage-sensitive dyes and Ca indicators, respectively. This powerful tool has rapidly become indispensable in the field of cardiac electrophysiology for studying depolarization wave propagation, estimating the conduction velocity of electrical impulses, and measuring Ca dynamics in cardiac cells and tissues. In addition, mapping these electrophysiological parameters is important for understanding cardiac arrhythmia mechanisms. In this review, we delve into the fundamentals of cardiac optical mapping technology and its applications when applied to hiPSC-derived cardiomyocytes and discuss related advantages and challenges. We also provide a detailed description of the processing and analysis of optical mapping data, which is a crucial step in the study of cardiac diseases and arrhythmia mechanisms for extracting and comparing relevant electrophysiological parameters.
Topics: Humans; Myocytes, Cardiac; Induced Pluripotent Stem Cells; Heart Diseases; Cardiac Electrophysiology; Coloring Agents
PubMed: 37681899
DOI: 10.3390/cells12172168 -
Proceedings of the National Academy of... Jun 2023Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since...
Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since dietary habits are inherently local and personal, any shift toward healthy and sustainable diets going against this identity will have an uphill road. Therefore, research should address the tension between the local and global nature of the biophysical (health, environment) and social dimensions (culture, economy). Advancing the food system transformation to healthy, sustainable diets transcends the personal control of engaging consumers. The challenge for science is to scale-up, to become more interdisciplinary, and to engage with policymakers and food system actors. This will provide the evidential basis to shift from the current narrative of price, convenience, and taste to one of health, sustainability, and equity. The breaches of planetary boundaries and the environmental and health costs of the food system can no longer be considered externalities. However, conflicting interests and traditions frustrate effective changes in the human-made food system. Public and private stakeholders must embrace social inclusiveness and include the role and accountability of all food system actors from the microlevel to the macrolevel. To achieve this food transformation, a new "social contract," led by governments, is needed to redefine the economic and regulatory power balance between consumers and (inter)national food system actors.
Topics: Humans; Diet; Health Status; Food; Biophysics; Government
PubMed: 37307436
DOI: 10.1073/pnas.2219272120