Cells can enter into a dormant state when faced with unfavorable conditions. However, how cells enter into and recover from this state is still poorly understood. Here, we study dormancy in different eukaryotic organisms and find it to be associated with a significant decrease in the mobility of organelles and foreign tracer particles. We show that this reduced mobility is caused by an influx of protons and a marked acidification of the cytoplasm, which leads to widespread macromolecular assembly of proteins and triggers a transition of the cytoplasm to a solid-like state with increased mechanical stability. We further demonstrate that this transition is required for cellular survival under conditions of starvation. Our findings have broad implications for understanding alternative physiological states, such as quiescence and dormancy, and create a new view of the cytoplasm as an adaptable fluid that can reversibly transition into a protective solid-like state.DOI: http://dx.doi.org/10.7554/eLife.09347.001

Classical continuum mechanics is used extensively to predict the properties of nanoscale materials such as graphene. The bending rigidity, κ, is an important parameter that is used, for example, to predict the performance of graphene nanoelectromechanical devices and also ripple formation. Despite its importance, there is a large spread in the theoretical predictions of κ for few-layer graphene. We have used the snap-through behavior of convex buckled graphene membranes under the application of electrostatic pressure to determine experimentally values of κ for double-layer graphene membranes. We demonstrate how to prepare convex-buckled suspended graphene ribbons and fully clamped suspended membranes and show how the determination of the curvature of the membranes and the critical snap-through voltage, using AFM, allows us to extract κ. The bending rigidity of bilayer graphene membranes under ambient conditions was determined to be 35.5−15.0 +20.0 eV. Monolayers are shown to have significantly lower κ than bilayers.

Based on a continuum mechanical model for single-layer graphene, we propose and analyze a microscopic mechanism for dissipation in nanoelectromechanical graphene resonators. We find that coupling between flexural modes and in-plane phonons leads to linear and nonlinear damping of out-of-plane vibrations. By tuning external parameters such as bias and ac voltages, one can cross over from a linear-to a nonlinear-damping dominated regime. We discuss the behavior of the effective quality factor in this context.

Video microscopy has a long history of providing insight and breakthroughs for a broad range of disciplines, from physics to biology. Image analysis to extract quantitative information from video microscopy data has traditionally relied on algorithmic approaches, which are often difficult to implement, time-consuming, and computationally expensive. Recently, alternative data-driven approaches using deep learning have greatly improved quantitative digital microscopy, potentially offering automatized, accurate, and fast image analysis. However, the combination of deep learning and video microscopy remains underutilized primarily due to the steep learning curve involved in developing custom deep-learning solutions. To overcome this issue, we introduce software, DeepTrack 2.0, to design, train, and validate deep-learning solutions for digital microscopy. We use this software to exemplify how deep learning can be employed for a broad range of applications, from particle localization, tracking, and characterization, to cell counting and classification. Thanks to its user-friendly graphical interface, DeepTrack 2.0 can be easily customized for user-specific applications, and thanks to its open-source, object-oriented programing, it can be easily expanded to add features and functionalities, potentially introducing deep-learning-enhanced video microscopy to a far wider audience.

We investigate the electromechanical coupling in 2d materials. For non-Bravais lattices, we find important corrections to the standard macroscopic strain -microscopic atomic-displacement theory. We put forward a general and systematic approach to calculate strain-displacement relations for several classes of 2d materials. We apply our findings to graphene as a study case, by combining a tight binding and a valence force-field model to calculate electronic and mechanical properties of graphene nanoribbons under strain. The results show good agreement with the predictions of the Dirac equation coupled to continuum mechanics. For this long wave-limit effective theory, we find that the strain-displacement relations lead to a renormalization correction to the strain-induced pseudo-magnetic fields. Implications for nanomechanical properties and electromechanical coupling in 2d materials are discussed.

We study circular nanomechanical graphene resonators by means of continuum elasticity theory, treating them as membranes. We derive dynamic equations for the flexural mode amplitudes. Due to the geometrical nonlinearity the mode dynamics can be modeled by coupled Duffing equations. By solving the Airy stress problem we obtain analytic expressions for the eigenfrequencies and nonlinear coefficients as functions of the radius, suspension height, initial tension, back-gate voltage and elastic constants, which we compare with finite element simulations. Using perturbation theory, we show that it is necessary to include the effects of the non-uniform stress distribution for finite deflections. This correctly reproduces the spectrum and frequency tuning of the resonator, including frequency crossings.

Label-free characterization of single biomolecules aims to complement fluorescence microscopy in situations where labeling compromises data interpretation, is technically challenging or even impossible. However, existing methods require the investigated species to bind to a surface to be visible, thereby leaving a large fraction of analytes undetected. Here, we present nanofluidic scattering microscopy (NSM), which overcomes these limitations by enabling label-free, real-time imaging of single biomolecules diffusing inside a nanofluidic channel. NSM facilitates accurate determination of molecular weight from the measured optical contrast and of the hydrodynamic radius from the measured diffusivity, from which information about the conformational state can be inferred. Furthermore, we demonstrate its applicability to the analysis of a complex biofluid, using conditioned cell culture medium containing extracellular vesicles as an example. We foresee the application of NSM to monitor conformational changes, aggregation and interactions of single biomolecules, and to analyze single-cell secretomes.

Thermalization in nonlinear systems is a central concept in statistical mechanics and has been extensively studied theoretically since the seminal work of Fermi, Pasta and Ulam (FPU). Using molecular dynamics and continuum modeling of a ring-down setup, we show that thermalization due to nonlinear mode coupling intrinsically limits the quality factor of nanomechanical graphene drums and turns them into potential test beds for FPU physics. We find the thermalization rate Γ to be independent of radius and scaling as Γ ∼ T * / 2 pre , where T * and pre are effective resonator temperature and prestrain.Advances in fabrication techniques enable production and characterization of one and two dimensional nanoscale mechanical resonators [1][2][3][4]. In particular, carbon-based resonators are considered to be promising for many applications due to their low mass and high quality factors (Q-factors) [5][6][7][8]. It is also known that these systems display strongly nonlinear behavior [4,9], which makes them interesting for investigations of nonlinear dynamics. The nonlinearities lead to a coupling between the vibrational modes [10,11]. This coupling allows for intermodal energy-transfer, which facilitates the redistribution of energy initially localized in a single mode.In this respect, the mode-coupling provides a dissipation channel for the fundamental mode (FM) dynamics. In contrast to other dissipation mechanisms previously studied in nanomechanical resonators [12][13][14][15][16][17], this is a fundamental intrinsic mechanism and therefore constitutes a lower limit on the relaxation rate of the FM. At finite temperatures, the effect of the mode couplings will be two-fold. First, they give rise to fluctuations in the resonator strain leading to dephasing or spectral broadening of the resonator [18]. Second, as we show in this Letter, they allow for energy redistribution among the modes. To distinguish the two effects we consider a ringdown setup, where the total energy of the resonator is conserved and the evolution of the spectral distribution of energy is monitored. This allows us to access the dynamics of the FM energy.The process of thermalization in a system of nonlinearly coupled oscillators was originally considered by Fermi, Pasta and Ulam (FPU) in their famous computer experiment in 1955 [19,20], and spawned an impressive amount of research that eventually resulted in the development of chaos theory [21] and the discovery of solitons [22]. For the FPU problem, it is known that above a certain critical energy density, energy initially fed into the FM is quickly redistributed among all modes, and the system approaches a thermal state. This threshold is connected to the onset of widespread chaos in the mode dynamics [20,21] and the stability of localized modes ("qbreathers") [23,24]. In recent years, the consensus has been reached that the main features observed in the FPU problem are not specific to the original model Hamiltonian [25,26]. A natural question, which is still under debate [27], is whether those f...