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Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic and…

Molecular Networks · Quantitative Biology 2019-01-31 Mona K. Tonn , Philipp Thomas , Mauricio Barahona , Diego A Oyarzún

Time-resolved single-molecule biophysical experiments yield data that contain a wealth of dynamic information, in addition to the equilibrium distributions derived from histograms of the time series. In typical force spectroscopic setups…

Biomolecules · Quantitative Biology 2011-07-14 Michael Hinczewski , Yann von Hansen , Roland R. Netz

Cellular heterogeneity is important to biological processes, including cancer and development. However, proteome heterogeneity is largely unexplored because of the limitations of existing methods for quantifying protein levels in single…

Genomics · Quantitative Biology 2018-10-29 Bogdan Budnik , Ezra Levy , Guillaume Harmange , Nikolai Slavov

Cellular functions are established through biological evolution, but are constrained by the laws of physics. For instance, the physics of protein folding limits the lengths of cellular polypeptide chains. Consequently, many cellular…

Biological Physics · Physics 2019-07-09 Pablo Sartori , Stanislas Leibler

Recent single-molecule pulling experiments have shown how it is possible to manipulate RNA molecules using optical tweezers force microscopy. We investigate a minimal model for the experimental setup which includes a RNA molecule connected…

Statistical Mechanics · Physics 2009-11-10 Maria Manosas , Felix Ritort

A simple way to get insights about the possible functional motions of a protein is to perform a normal mode analysis (NMA). Indeed, it has been shown that low-frequency modes thus obtained are often closely related to domain motions…

Biomolecules · Quantitative Biology 2013-12-20 Yves-Henri Sanejouand

Mechanical characteristics of single biological cells are used to identify and possibly leverage interesting differences among cells or cell populations. Fluidity---hysteresivity normalized to the extremes of an elastic solid or a viscous…

Cell Behavior · Quantitative Biology 2013-10-22 John M. Maloney , Eric Lehnhardt , Alexandra F. Long , Krystyn J. Van Vliet

Cooperativity is a hallmark of proteins, many of which show a modular architecture comprising discrete structural domains. Detecting and describing dynamic couplings between structural regions is difficult in view of the many-body nature of…

Biological Physics · Physics 2015-02-03 Olga Kononova , Lee Jones , Valeri Barsegov

We present an alternative approach to pump-probe spectroscopy for measuring fast charge dynamics with an atomic force microscope (AFM). Our approach is based on coherent multifrequency lock-in measurement of the intermodulation between a…

Mesoscale and Nanoscale Physics · Physics 2019-01-30 Riccardo Borgani , David B. Haviland

Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and…

Soft Condensed Matter · Physics 2007-12-06 Michael Bachmann , Wolfhard Janke

The dynamics of molecular motors which occasionally detach from a heterogeneous track like DNA or RNA is considered. Motivated by recent single molecule experiments, we study a simple model for a motor moving along a disordered track using…

Statistical Mechanics · Physics 2009-11-10 Yariv Kafri , David K. Lubensky , David R. Nelson

We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…

Disordered Systems and Neural Networks · Physics 2008-02-03 T. Garel , H. Orland , E. Pitard

Heteropolymers are ubiquitous in both synthetic systems, such as block copolymers, and biological macromolecules, including proteins and nucleic acids. Beyond their chemical composition, these polymers often exhibit spatial variations in…

Soft Condensed Matter · Physics 2025-04-02 Arvind Saini , Rajiblochan Sahoo , Rajarshi Chakrabarti , Sayantan Dutta

Atomic force microscopy (AFM) is one of the most promising methods for investigating the structure of materials at the micro and nanoscale levels, as well as their local physical-mechanical properties. The experimental data obtained with…

Materials Science · Physics 2018-05-07 Oleg K. Garishin , Roman I. Izyumov , Alexander L. Svistkov

Single molecule force spectroscopy provide details of the underlying energy surfaces of proteins which are essential to the understanding of their unfolding process. Recently, it has been observed experimentally that by pulling proteins in…

Statistical Mechanics · Physics 2009-11-13 R. Rajesh , D. Giri , I. Jensen , S. Kumar

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

Soft Condensed Matter · Physics 2010-10-19 Pragya Shukla

A main goal of single-molecule experiments is to evaluate equilibrium free energy differences by applying fluctuation relations to repeated work measurements along irreversible processes. We quantify the error that is made in a free energy…

Statistical Mechanics · Physics 2009-06-22 Alessandro Mossa , Sara de Lorenzo , Josep Maria Huguet , Felix Ritort

Cell populations are never truly homogeneous; individual cells exist in biochemical states that define functional differences between them. New technology based on microfluidic arrays combined with multiplexed quantitative polymerase chain…

Single-molecule detection enables direct observation of individual biomolecular events, providing mechanistic insights into biological processes and offering a powerful tool for disease diagnostics. However, the fundamental scale mismatch…

Optics · Physics 2025-10-14 Guifeng Li , Chaoyang Gong

Cell stiffness is a key determinant of how cells deform, migrate, and adapt to mechanically restrictive environments, yet existing single-cell stiffness assays remain difficult to combine with molecular analysis and downstream functional…

Cell Behavior · Quantitative Biology 2026-04-02 Yuhao Zhang , Luyao Zhao , Zhengfu Huang , Kenan Song , Xianqiao Wang , Xianyan Chen , Jin Xie , Yiping Zhao , He Li , Leidong Mao , Yong Teng , Yang Liu