-
BioRxiv : the Preprint Server For... Sep 2023We propose to capture reaction-diffusion on a molecule-by-molecule basis from the fastest acquirable timescale, namely individual photon arrivals. We illustrate our...
We propose to capture reaction-diffusion on a molecule-by-molecule basis from the fastest acquirable timescale, namely individual photon arrivals. We illustrate our method on intrinsically disordered human proteins, the linker histone H1.0 as well as its chaperone prothymosin , as these diffuse through an illuminated confocal spot and interact forming larger ternary complexes on millisecond timescales. Most importantly, single-molecule reaction-diffusion, smRD, reveals single molecule properties without trapping or otherwise confining molecules to surfaces. We achieve smRD within a Bayesian paradigm and term our method Bayes-smRD. Bayes-smRD is further free of the average, bulk, results inherent to the analysis of long photon arrival traces by fluorescence correlation spectroscopy. In learning from thousands of photon arrivals continuous spatial positions and discrete conformational and photophysical state changes, Bayes-smRD estimates kinetic parameters on a molecule-by-molecule basis with two to three orders of magnitude less data than tools such as fluorescence correlation spectroscopy thereby also dramatically reducing sample photodamage.
PubMed: 37732202
DOI: 10.1101/2023.09.05.556378 -
Neuroscience and Biobehavioral Reviews Mar 2023Several authors have proposed that perceptual information carries labels that identify temporal features, including time of occurrence, ordinal temporal relations, and... (Review)
Review
Several authors have proposed that perceptual information carries labels that identify temporal features, including time of occurrence, ordinal temporal relations, and brief durations. These labels serve to locate and organise perceptual objects, features, and events in time. In some proposals time marking has local, specific functions such as synchronisation of different features in perceptual processing. In other proposals time marking has general significance and is responsible for rendering perceptual experience temporally coherent, just as various forms of spatial information render the visual environment spatially coherent. These proposals, which all concern time marking on the millisecond time scale, are reviewed. It is concluded that time marking is vital to the construction of a multisensory perceptual world in which things are orderly with respect to both space and time, but that much more research is needed to ascertain its functions in perception and its neurophysiological foundations.
Topics: Humans; Visual Perception; Time Factors; Photic Stimulation; Acoustic Stimulation; Time Perception; Auditory Perception
PubMed: 36642288
DOI: 10.1016/j.neubiorev.2023.105043 -
Proceedings of the National Academy of... Sep 2020A now substantial body of science implicates a dynamic interplay between genetic and environmental variation in the development of individual differences in behavior and...
A now substantial body of science implicates a dynamic interplay between genetic and environmental variation in the development of individual differences in behavior and health. Such outcomes are affected by molecular, often epigenetic, processes involving gene-environment (G-E) interplay that can influence gene expression. Early environments with exposures to poverty, chronic adversities, and acutely stressful events have been linked to maladaptive development and compromised health and behavior. Genetic differences can impart either enhanced or blunted susceptibility to the effects of such pathogenic environments. However, largely missing from present discourse regarding G-E interplay is the role of time, a "third factor" guiding the emergence of complex developmental endpoints across different scales of time. Trajectories of development increasingly appear best accounted for by a complex, dynamic interchange among the highly linked elements of genes, contexts, and time at multiple scales, including neurobiological (minutes to milliseconds), genomic (hours to minutes), developmental (years and months), and evolutionary (centuries and millennia) time. This special issue of PNAS thus explores time and timing among G-E transactions: The importance of timing and timescales in plasticity and critical periods of brain development; epigenetics and the molecular underpinnings of biologically embedded experience; the encoding of experience across time and biological levels of organization; and gene-regulatory networks in behavior and development and their linkages to neuronal networks. Taken together, the collection of papers offers perspectives on how G-E interplay operates contingently within and against a backdrop of time and timescales.
Topics: Animals; Biological Evolution; Epigenesis, Genetic; Gene Expression Regulation; Gene-Environment Interaction; Humans; Time
PubMed: 32967067
DOI: 10.1073/pnas.2016710117 -
Optics Express Aug 2021Single-molecule spectroscopy has been extensively used to investigate heterogeneity in static and dynamic behaviors on millisecond and second timescales. More recently,...
Single-molecule spectroscopy has been extensively used to investigate heterogeneity in static and dynamic behaviors on millisecond and second timescales. More recently, single-molecule pump-probe spectroscopy emerged as a method to access heterogeneity on the femtosecond and picosecond timescales. Here, we develop a single-molecule pump-probe apparatus that is easily tunable across the visible region and demonstrate its utility on the widely-used fluorescent dye, Atto647N. A spectrally-independent, bimodal distribution of energetic relaxation time constants is found, where one peak corresponds to electronic dephasing (∼ 100 fs) and the other to intravibrational relaxation (∼ 300 fs). The bimodal nature indicates that relaxation within each individual molecule is dominated by only one of these processes. Both peaks of the distribution are narrow, suggesting little heterogeneity is present for either process. As illustrated here, spectrally-tunable single-molecule pump-probe spectroscopy will enable investigation of the heterogeneity in a wide range of biological and material systems.
PubMed: 34614960
DOI: 10.1364/OE.432995 -
Cell Reports Oct 2019Recent rapid progress in the field of mechanobiology has been driven by novel emerging tools and methodologies and growing interest from different scientific... (Review)
Review
Recent rapid progress in the field of mechanobiology has been driven by novel emerging tools and methodologies and growing interest from different scientific disciplines. Specific progress has been made toward understanding how cell mechanics is linked to intracellular signaling and the regulation of gene expression in response to a variety of mechanical stimuli. There is a direct link between the mechanoreceptors at the cell surface and intracellular biochemical signaling, which in turn controls downstream effector molecules. Among the mechanoreceptors in the cell membrane, mechanosensitive (MS) ion channels are essential for the ultra-rapid (millisecond) transduction of mechanical stimuli into biologically relevant signals. The three decades of research on mechanosensitive channels resulted in the formulation of two basic principles of mechanosensitive channel gating: force-from-lipids and force-from-filament. In this review, we revisit the biophysical principles that underlie the innate force-sensing ability of mechanosensitive channels as contributors to the force-dependent evolution of life forms.
Topics: Animals; Biophysics; Cell Membrane; Humans; Ion Channels; Mechanoreceptors; Mechanotransduction, Cellular; Signal Transduction
PubMed: 31577940
DOI: 10.1016/j.celrep.2019.08.075