biophysics   333

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Membranes to Molecular Machines: Active Matter and the Remaking of Life, Grote
"Today's science tells us that our bodies are filled with molecular machinery that orchestrates all sorts of life processes. When we think, microscopic "channels" open and close in our brain cell membranes; when we run, tiny "motors" spin in our muscle cell membranes; and when we see, light operates "molecular switches" in our eyes and nerves. A molecular-mechanical vision of life has become commonplace in both the halls of philosophy and the offices of drug companies, where researchers are developing “proton pump inhibitors” or medicines similar to Prozac.
"Membranes to Molecular Machines explores just how late twentieth-century science came to think of our cells and bodies this way. This story is told through the lens of membrane research, an unwritten history at the crossroads of molecular biology, biochemistry, physiology, and the neurosciences, that directly feeds into today's synthetic biology as well as nano- and biotechnology. Mathias Grote shows how these sciences not only have made us think differently about life, they have, by reworking what membranes and proteins represent in laboratories, allowed us to manipulate life as "active matter" in new ways. Covering the science of biological membranes in the United States and Europe from the mid-1960s to the 1990s, this book connects that history to contemporary work with optogenetics, a method for stimulating individual neurons using light, and will enlighten and provoke anyone interested in the intersection of chemical research and the life sciences—from practitioner to historian to philosopher."
to:NB  books:noted  history_of_science  molecular_biology  biophysics 
20 days ago by cshalizi
Rev. Mod. Phys. 91, 031001 (2019) - Colloquium: Proteins: The physics of amorphous evolving matter
"Protein is matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with diverse biochemistry. But it is also a point along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism, and the population. A physical theory of proteins therefore needs to unify both aspects, the biophysical and the evolutionary. Specifically, it should provide a model of how the DNA gene is mapped into the functional phenotype of the protein. Several physical approaches to the protein problem are reviewed, focusing on a mechanical framework which treats proteins as evolvable condensed matter: Mutations introduce localized perturbations in the gene, which are translated to localized perturbations in the protein matter. A natural tool to examine how mutations shape the phenotype are Green’s functions. They map the evolutionary linkage among mutations in the gene (termed epistasis) to cooperative physical interactions among the amino acids in the protein. The mechanistic view can be applied to examine basic questions of protein evolution and design."

--- Ungated:
to:NB  biophysics  evolutionary_biology  eckmann.jean-pierre 
23 days ago by cshalizi
[1907.03891] Quantitative Immunology for Physicists
"The adaptive immune system is a dynamical, self-organized multiscale system that protects vertebrates from both pathogens and internal irregularities, such as tumours. For these reason it fascinates physicists, yet the multitude of different cells, molecules and sub-systems is often also petrifying. Despite this complexity, as experiments on different scales of the adaptive immune system become more quantitative, many physicists have made both theoretical and experimental contributions that help predict the behaviour of ensembles of cells and molecules that participate in an immune response. Here we review some recent contributions with an emphasis on quantitative questions and methodologies. We also provide a more general methods section that presents some of the wide array of theoretical tools used in the field."
to:NB  immunology  signal_transduction  biology  biophysics 
23 days ago by cshalizi
[1906.08154] Stochastic thermodynamics and modes of operation of ribosome: A network theoretic perspective
"The ribosome is one of the largest and most complex macromolecular machines in living cells. It polymerizes a specific protein in a step-by-step manner as directed by the corresponding template messenger RNA (mRNA) and this process is referred to as `translation' of the genetic message encoded in the sequence of mRNA transcript. In each successful chemo-mechanical cycle during the (protein) elongation stage, the ribosome elongates the protein by a single subunit, called amino acid, and steps forward on the template mRNA by three nucleotides called a codon. Therefore, a ribosome is also regarded as a molecular motor for which the mRNA serves as the track, its step size is that of a codon and two molecules of GTP hydrolyzed in that cycle serve as its fuel. What adds further complexity is the existence of branched pathways and futile consumption of fuel that leads neither to elongation of the nascent protein nor forward stepping of the ribosome on its track. We investigate a model based on the network of the seven discrete chemo-mechanical states of a ribosome using a graph-theoretic approach to derive the exact solution of the corresponding master equations. We identify the various possible modes of operation of a ribosome in terms of its average velocity and mean rate of GTP hydrolysis. We also discuss the stochastic thermodynamics of a ribosome by computing entropy production as functions of the rates of the interstate transitions."

--- "Network theory", on an admittedly cursory glance, seems to just be "analyzing a finite Markov chain", but this might be worth mining for an example when teaching Markov chains...
to:NB  biophysics  molecular_biology  thermodynamics  markov_models  to_teach:data_over_space_and_time 
8 weeks ago by cshalizi
[1705.00721] Single microtubules and small networks become significantly stiffer on short time-scales upon mechanical stimulation
The transfer of mechanical signals through cells is a complex phenomenon. To uncover a new mechanotransduction pathway, we study the frequency-dependent transport of mechanical stimuli by single microtubules and small networks in a bottom-up approach using optically trapped beads as anchor points. We interconnected microtubules to linear and triangular geometries to perform micro-rheology by defined oscillations of the beads relative to each other. We found a substantial stiffening of single filaments above a characteristic transition frequency of 1-30 Hz depending on the filament's molecular composition. Below this frequency, filament elasticity only depends on its contour and persistence length. Interestingly, this elastic behavior is transferable to small networks, where we found the surprising effect that linear two filament connections act as transistor-like, angle dependent momentum filters, whereas triangular networks act as stabilizing elements. These observations implicate that cells can tune mechanical signals by temporal and spatial filtering stronger and more flexibly than expected.
phrasing!  biophysics  cytoskeleton  microtubules  structural-biology  nanotechnology  rather-interesting  experiment  looking-to-see 
10 weeks ago by Vaguery
Unveiling the Active Nature of Living-Membrane Fluctuations and Mechanics | Annual Review of Condensed Matter Physics
"Soft-condensed matter physics has provided, in the past decades, many of the relevant concepts and methods allowing successful description of living cells and biological tissues. This recent quantitative physical description of biological systems has profoundly advanced our understanding of life, which is shifting from a descriptive to a predictive level. Like other active materials investigated in condensed matter physics, biological materials still pose great challenges to modern physics as they form a specific class of nonequilibrium systems. Actively driven membranes have been studied for more than two decades, taking advantage of rapid progress in membrane physics and in the experimental development of reconstituted active membranes. The physical description of activity within living biological membranes remains, however, a key challenge that animates a dynamic research community, bringing together physicists and biologists. Here, we first review the past two decades of experimental and theoretical advances that enabled the characterization of mechanical properties and nonequilibrium fluctuations in active membranes. We distinguish active processes originating from membrane proteins or from external interactions, such as cytoskeletal forces. Then, we focus on the emblematic case of red blood cell flickering, the active origin of which has been debated for decades until recently. We finally close this review by discussing future challenges in this ever more interdisciplinary field."
to:NB  biophysics  condensed_matter  physics  non-equilibrium 
12 weeks ago by cshalizi
Why the Wheel Is Round: Muscles, Technology, and How We Make Things Move, Vogel
"There is no part of our bodies that fully rotates—be it a wrist or ankle or arm in a shoulder socket, we are made to twist only so far. And yet there is no more fundamental human invention than the wheel—a rotational mechanism that accomplishes what our physical form cannot. Throughout history, humans have developed technologies powered by human strength, complementing the physical abilities we have while overcoming our weaknesses. Providing a unique history of the wheel and other rotational devices—like cranks, cranes, carts, and capstans—Why the Wheel Is Round examines the contraptions and tricks we have devised in order to more efficiently move—and move through—the physical world.
"Steven Vogel combines his engineering expertise with his remarkable curiosity about how things work to explore how wheels and other mechanisms were, until very recently, powered by the push and pull of the muscles and skeletal systems of humans and other animals. Why the Wheel Is Round explores all manner of treadwheels, hand-spikes, gears, and more, as well as how these technologies diversified into such things as hand-held drills and hurdy-gurdies.  Surprisingly, a number of these devices can be built out of everyday components and materials, and Vogel’s accessible and expansive book includes instructions and models so that inspired readers can even attempt to make their own muscle-powered technologies, like trebuchets and ballista.
"Appealing to anyone fascinated by the history of mechanics and technology as well as to hobbyists with home workshops, Why the Wheel Is Round offers a captivating exploration of our common technological heritage based on the simple concept of rotation. From our leg muscles powering the gears of a bicycle to our hands manipulating a mouse on a roller ball, it will be impossible to overlook the amazing feats of innovation behind our daily devices."
to:NB  books:noted  popular_science  biology  biophysics  engineering  how_stuff_works 
november 2018 by cshalizi
Zocchi, G.: Molecular Machines: A Materials Science Approach (Hardcover and eBook) | Princeton University Press
"Molecular Machines presents a dynamic new approach to the physics of enzymes and DNA from the perspective of materials science. Unified around the concept of molecular deformability—how proteins and DNA stretch, fold, and change shape—this book describes the complex molecules of life from the innovative perspective of materials properties and dynamics, in contrast to structural or purely chemical approaches. It covers a wealth of topics, including nonlinear deformability of enzymes and DNA; the chemo-dynamic cycle of enzymes; supra-molecular constructions with internal stress; nano-rheology and viscoelasticity; and chemical kinetics, Brownian motion, and barrier crossing. Essential reading for researchers in materials science, engineering, and nanotechnology, the book also describes the landmark experiments that have established the materials properties and energy landscape of large biological molecules.
"Molecular Machines is also ideal for the classroom. It gives graduate students a working knowledge of model building in statistical mechanics, making it an essential resource for tomorrow's experimentalists in this cutting-edge field. In addition, mathematical methods are introduced in the bio-molecular context—for example, DNA conformational transitions are used to illustrate the transfer matrix formalism. The result is a generalized approach to mathematical problem solving that enables students to apply their findings more broadly."
to:NB  books:noted  biophysics  molecular_biology 
august 2018 by cshalizi
Nicolas Rashevsky's Mathematical Biophysics | SpringerLink
"This paper explores the work of Nicolas Rashevsky, a Russian émigré theoretical physicist who developed a program in “mathematical biophysics” at the University of Chicago during the 1930s. Stressing the complexity of many biological phenomena, Rashevsky argued that the methods of theoretical physics – namely mathematics – were needed to “simplify” complex biological processes such as cell division and nerve conduction. A maverick of sorts, Rashevsky was a conspicuous figure in the biological community during the 1930s and early 1940s: he participated in several Cold Spring Harbor symposia and received several years of funding from the Rockefeller Foundation. However, in contrast to many other physicists who moved into biology, Rashevsky's work was almost entirely theoretical, and he eventually faced resistance to his mathematical methods. Through an examination of the conceptual, institutional, and scientific context of Rashevsky's work, this paper seeks to understand some of the reasons behind this resistance."
to:NB  to_read  history_of_science  history_of_physics  history_of_biology  biology  biophysics  complexity  rashevsky.nicolas  via:? 
july 2018 by cshalizi
Real-space and real-time dynamics of CRISPR-Cas9 visualized by high-speed atomic force microscopy | Nature Communications
The CRISPR-associated endonuclease Cas9 binds to a guide RNA and cleaves double-stranded DNA with a sequence complementary to the RNA guide. The Cas9–RNA system has been harnessed for numerous applications, such as genome editing. Here we use high-speed atomic force microscopy (HS-AFM) to visualize the real-space and real-time dynamics of CRISPR-Cas9 in action. HS-AFM movies indicate that, whereas apo-Cas9 adopts unexpected flexible conformations, Cas9–RNA forms a stable bilobed structure and interrogates target sites on the DNA by three-dimensional diffusion. These movies also provide real-time visualization of the Cas9-mediated DNA cleavage process. Notably, the Cas9 HNH nuclease domain fluctuates upon DNA binding, and subsequently adopts an active conformation, where the HNH active site is docked at the cleavage site in the target DNA. Collectively, our HS-AFM data extend our understanding of the action mechanism of CRISPR-Cas9.

See also, the video at and a readable layperson overview at
genetics  crispr  cas9  visualization  enzymes  xraycrystallography  biophysics  video 
november 2017 by drmeme
RT : Detecting sequence defects by supercoiling DNA with magnetic tweezers. Use to sense damage in vivo?
biophysics  from twitter
october 2017 by _1134
[1109.6459] Folding Kinetics of a Polymer
By simulating the first order globule-crystal transition of a flexible homopolymer chain, both by collision dynamics and Monte Carlo with non-kinetic moves, we show that the effective and the thermodynamic transition temperatures are different and we propose a way of quantifying the kinetic hindering. We then also observe that the top eigenvalue in the spectrum of the dynamical (contact or adjacency) matrix provides insight into the ensembles of folding and unfolding trajectories, and may be a suitable additional reaction coordinate for the folding transition of chain molecules.
lattice-proteins  biophysics  structural-biology  simulation  energy-landscapes  to-write-about  rather-interesting  feature-construction 
september 2017 by Vaguery
Differential Strengths Of Molecular Determinants Guide Environment Specific Mutational Fates | bioRxiv
Under the influence of selection pressures imposed by natural environments, organisms maintain competitive fitness through underlying molecular evolution of individual genes across the genome. For molecular evolution, how multiple interdependent molecular constraints play a role in determination of fitness under different environmental conditions is largely unknown. Here, using Deep Mutational Scanning (DMS), we quantitated empirical fitness of ~2000 single site mutants of Gentamicin-resistant gene (GmR). This enabled a systematic investigation of effects of different physical and chemical environments on the fitness landscape of the gene. Molecular constraints of the fitness landscapes seem to bear differential strengths in an environment dependent manner. Among them, conformity of the identified directionalities of the environmental selection pressures with known effects of the environments on protein folding proves that along with substrate binding, protein stability is the common strong constraint of the fitness landscape. Our study thus provides mechanistic insights into the molecular constraints that allow accessibility of mutational fates in environment dependent manner.
contingency  fitness-landscapes  biophysics  evolutionary-algorithms  structure-function-relations  climb-the-citation-tree  to-write-about  to-understand 
september 2017 by Vaguery
Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers
Today’s lifeforms are based on informational polymers, namely proteins and nucleic acids. It is thought that simple chemical processes on the early earth could have polymerized monomer units into short random sequences. It is not clear, however, what physical process could have led to the next level—to longer chains having particular sequences that could increase their own concentrations. We study polymers of hydrophobic and polar monomers, such as today’s proteins. We find that even some random sequence short chains can collapse into compact structures in water, with hydrophobic surfaces that can act as primitive catalysts, and that these could elongate other chains. This mechanism explains how random chemical polymerizations could have given rise to longer sequence-dependent protein-like catalytic polymers.
lattice-polymers  biophysics  self-organization  origin-of-life  simulation  rather-interesting  to-write-about  molecular-design  molecular-machinery 
september 2017 by Vaguery
Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers
"It is not known how life originated. It is thought that prebiotic processes were able to synthesize short random polymers. However, then, how do short-chain molecules spontaneously grow longer? Also, how would random chains grow more informational and become autocatalytic (i.e., increasing their own concentrations)? We study the folding and binding of random sequences of hydrophobic (HH) and polar (PP) monomers in a computational model. We find that even short hydrophobic polar (HP) chains can collapse into relatively compact structures, exposing hydrophobic surfaces. In this way, they act as primitive versions of today’s protein catalysts, elongating other such HP polymers as ribosomes would now do. Such foldamer catalysts are shown to form an autocatalytic set, through which short chains grow into longer chains that have particular sequences. An attractive feature of this model is that it does not overconverge to a single solution; it gives ensembles that could further evolve under selection. This mechanism describes how specific sequences and conformations could contribute to the chemistry-to-biology (CTB) transition."
to:NB  biophysics  polymers  origin_of_life  self-organization 
september 2017 by cshalizi

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