The elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. However, accurate quantification of their elastic modulus is challenging due to their nanoscale dimensions and their fluid-like lipid bilayer. We show that the previous attempts to develop atomic force microscopy-based protocol are flawed as they lack theoretical underpinning as well as ignore important contributions arising from the surface adhesion forces and membrane fluctuations. We develop a protocol comprising a theoretical framework, experimental technique, and statistical approach to accurately quantify the bending and elastic modulus of EVs. The method reveals that membrane fluctuations play a dominant role even for a single EV. The method is then applied to EVs derived from human embryonic kidney cells and their genetically engineered classes altering the tetraspanin expression. The data show a large spread; the area modulus is in the range of 4 to 19 mN/m and the bending modulus is in the range of 15 to 33 kBT, respectively. Surprisingly, data for a single EV, revealed by repeated measurements, also show a spread that is attributed to their compositionally heterogeneous fluid membrane and thermal effects. Our protocol uncovers the influence of membrane protein alterations on the elastic modulus of EVs.

We use the short-time inference scheme [Manikandan, Phys. Rev. Lett. 124, 120603 (2020)0031-900710.1103/PhysRevLett.124.120603], obtained within the framework of stochastic thermodynamics, to infer a lower bound to entropy production rate from flickering data generated by interference reflection microscopy of HeLa cells. We can clearly distinguish active cell membranes from their adenosine-triphosphate-depleted selves and even spatiotemporally resolve activity down to the scale of about 1 μm. Our estimate of activity is model independent.

Elastic turbulence is the chaotic fluid motion resulting from elastic instabilities due to the addition of polymers in small concentrations at very small Reynolds (Re) numbers. Our direct numerical simulations show that elastic turbulence, though a low Re phenomenon, has more in common with classical, Newtonian turbulence than previously thought. In particular, we find power-law spectra for kinetic energy E(k) ~ k−4 and polymeric energy Ep(k) ~ k−3/2, independent of the Deborah (De) number. This is further supported by calculation of scale-by-scale energy budget which shows a balance between the viscous term and the polymeric term in the momentum equation. In real space, as expected, the velocity field is smooth, i.e., the velocity difference across a length scale r, δu ~ r but, crucially, with a non-trivial sub-leading contribution r3/2 which we extract by using the second difference of velocity. The structure functions of second difference of velocity up to order 6 show clear evidence of intermittency/multifractality. We provide additional evidence in support of this intermittent nature by calculating moments of rate of dissipation of kinetic energy averaged over a ball of radius r, εr, from which we compute the multifractal spectrum.

Red blood cells (RBCs) are more deformable than most other cells in the body, and any change in the deformability of RBCs can have major physiological effects. Here, we report a high-throughput micro- fluidic device to determine the Young's modulus of single RBCs. Our device consists of a single channel opening into a funnel, with a semi-circular obstacle placed at the mouth of the funnel. As an RBC passes the obstacle, it deflects from its original path. Using populations of artificially stiffened RBCs, we show that the stiffer RBCs deflect more compared to the healthy RBCs. We then generate a calibration curve that maps each RBC trajectory to its Young's modulus, obtained using an atomic force microscope. Finally, we sort a mixed population of RBCs based on their deformability alone. Our device could potentially be further miniaturized to sort and obtain the elastic constants of nanoscale objects, such as exosomes, whose shape change is difficult to monitor by optical microscopy.

Adherent cells ensure membrane homeostasis during de-adhesion by various mechanisms, including endocytosis. Although mechano-chemical feedbacks involved in this process have been studied, the step-by-step build-up and resolution of the mechanical changes by endocytosis are poorly understood. To investigate this, we studied the de-adhesion of HeLa cells using a combination of interference reflection microscopy, optical trapping and fluorescence experiments. We found that de-adhesion enhanced membrane height fluctuations of the basal membrane in the presence of an intact cortex. A reduction in the tether force was also noted at the apical side. However, membrane fluctuations reveal phases of an initial drop in effective tension followed by saturation. The area fractions of early (Rab5-labelled) and recycling (Rab4-labelled) endosomes, as well as transferrin-labelled pits close to the basal plasma membrane, also transiently increased. On blocking dynamin-dependent scission of endocytic pits, the regulation of fluctuations was not blocked, but knocking down AP2-dependent pit formation stopped the tension recovery. Interestingly, the regulation could not be suppressed by ATP or cholesterol depletion individually but was arrested by depleting both. The data strongly supports Clathrin and AP2-dependent pit-formation to be central to the reduction in fluctuations confirmed by super-resolution microscopy. Furthermore, we propose that cholesterol-dependent pits spontaneously regulate tension under ATP-depleted conditions.

Lagrangian pair dispersion provides insights into mixing in turbulent flows. By direct numerical simulations (DNSs) we show that the statistics of pair dispersion in the randomly forced two-dimensional Burgers equation, which is a typical model of shock-dominated turbulence, is very different from its incompressible counterpart because Lagrangian particles get trapped in shocks. We develop a heuristic theoretical framework that accounts for this - a generalization of the multifractal model - whose prediction of the scaling of Lagrangian exit times agrees well with our DNS.

We study the buckling of pressurized spherical shells by Monte Carlo simulations in which the detailed balance is explicitly broken - thereby driving the shell to be active, out of thermal equilibrium. Such a shell typically has either higher (active) or lower (sedate) fluctuations compared to one in thermal equilibrium depending on how the detailed balance is broken. We show that, for the same set of elastic parameters, a shell that is not buckled in thermal equilibrium can be buckled if turned active. Similarly a shell that is buckled in thermal equilibrium can unbuckle if sedated. Based on this result, we suggest that it is possible to experimentally design microscopic elastic shells whose buckling can be optically controlled.

We carry out a detailed study of dynamic multiscaling in the turbulent nonequilibrium, but statistically steady, state of the stochastically forced one-dimensional Burgers equation. We introduce the concept of interval collapse time, which we define as the time taken for a spatial interval, demarcated by a pair of Lagrangian tracers, to collapse at a shock. By calculating the dynamic scaling exponents of the moments of various orders of these interval collapse times, we show that (a) there is not one but an infinity of characteristic time scales and (b) the probability distribution function of the interval collapse times is non-Gaussian and has a power-law tail. Our study is based on (a) a theoretical framework that allows us to obtain dynamic-multiscaling exponents analytically, (b) extensive direct numerical simulations, and (c) a careful comparison of the results of (a) and (b). We discuss possible generalizations of our work to higher dimensions, for the stochastically forced Burgers equation, and to other compressible flows that exhibit turbulence with shocks.

Motivated by wind blowing over water, we use asymptotic methods to study the evolution of short wavelength interfacial waves driven by the combined action of these flows. We solve the Rayleigh equation for the stability of the shear flow, and construct a uniformly valid approximation for the perturbed streamfunction, or eigenfunction. We then expand the real part of the eigenvalue, the phase speed, in a power series of the inverse wavenumber and show that the imaginary part is exponentially small. We give expressions for the growth rates of the Miles (J. Fluid Mech., vol. 3, 1957, pp. 185-204) and rippling (e.g. Young & Wolfe, J. Fluid Mech., vol. 739, 2014, pp. 276-307) instabilities that are valid for an arbitrary shear flow. The accuracy of the results is demonstrated by a comparison with the exact solution of the eigenvalue problem in the case when both the wind and the current have an exponential profile.

The Sun's activity, which is associated with the solar magnetic cycle, creates a dynamic environment in space known as space weather. Severe space weather can disrupt space-based and Earth-based technologies. Slow decadal-scale variations on solar-cycle timescales are important for radiative forcing of the Earth's atmosphere and impact satellite lifetimes and atmospheric dynamics. Predicting the solar magnetic cycle is therefore of critical importance for humanity. In this context, a novel development is the application of machine-learning algorithms for solar-cycle forecasting. Diverse approaches have been developed for this purpose; however, with no consensus across different techniques and physics-based approaches. Here, we first explore the performance of four different machine-learning algorithms - all of them belonging to a class called Recurrent Neural Networks (RNNs) - in predicting simulated sunspot cycles based on a widely studied, stochastically forced, nonlinear time-delay solar dynamo model. We conclude that the algorithm Echo State Network (ESN) performs the best, but predictability is limited to only one future sunspot cycle, in agreement with recent physical insights. Subsequently, we train the ESN algorithm and a modified version of it (MESN) with solar-cycle observations to forecast Cycles 22 - 25. We obtain accurate hindcasts for Solar Cycles 22 - 24. For Solar Cycle 25 the ESN algorithm forecasts a peak amplitude of 131 +/- 14 sunspots around July 2024 and indicates a cycle length of approximately 10 years. The MESN forecasts a peak of 137 +/- 2 sunspots around April 2024, with the same cycle length. Qualitatively, both forecasts indicate that Cycle 25 will be slightly stronger than Cycle 24 but weaker than Cycle 23. Our novel approach bridges physical model-based forecasts with machine-learning-based approaches, achieving consistency across these diverse techniques.