Linear microrheology with optical tweezers of living cells 'is not an option'!

Optical tweezers have been successfully adopted as exceptionally sensitive transducers for microrheology studies of complex fluids. Despite the general trend, in this article I explain why a similar approach should not be adopted for microrheology studies of living cells. This conclusion is reached on the basis of statistical mechanics principles that indicate the unsuitability of optical tweezers for such purpose

Dynamics of semiflexible polymer solutions in the tightly entangled concentration regime

I corroborate an important experimental evidence reported by Schuldt et al. [ Phys. Rev. Lett. 2016, 117, 197801] revealing the incapability of the current theoretical framework to fully describe the dynamics of semiflexible polymer solutions in the tightly entangled concentration regime. These results have been endorsed here by means of previously published, but overlooked, data by Tassieri et al. [ Phys. Rev. Lett. 2008, 101, 198301; Biophys. J. 2008, 94, 2170]. The ensemble of information provides a strong evidence that the scaling law of the plateau modulus as a function of polymer’s concentration and persistence length, i.e., G0 ∝ cαLpβ, should have both the exponents positive, in contrast with all the existing predictions converging on similar values of α > 0 and β < 0—hence the need of new theoretical models able to better interpret the contribution of the polymer bending rigidity to the viscoelastic properties of the polymer network

Comment on "A symmetrical method to obtain shear moduli from microrheology" by Kengo Nishi, Maria L. Kilfoil, Christoph F. Schmidt, and F. C. MacKintosh, Soft Matter, 2018, 14, 3716

Nishi et al. have presented a new analytical method for transforming the time-dependent materials' compliance into their frequency-dependent complex shear modulus, without the need of a preconceived fitting function nor the use of Kramers–Kronig transformations. They claim that their method significantly improves the accuracy of the outcomes, especially at high frequencies, up to “almost” the Nyquist frequency. Here, I corroborate that their method is actually able to provide a close estimation of the materials' complex shear modulus over the ‘entire’ range of explored frequencies (i.e. beyond the Nyquist frequency), as long as the compliance values are linearly spaced in the time-domain and its value at time zero is included as the first data point in the input file. Moreover, as a means of comparison, I employ the analytical method introduced by Tassieri et al. [New J. Phys., 2012, 14, 115032] for performing the Fourier transform of any generic time-dependent function that vanishes for negative times, is sampled at a finite rate, need not be equally spaced and extends over a finite time window. This existing method does not need preconceived fitting functions nor the use of Kramers–Kronig transformations; yet it shows a higher degree of accuracy compared to the one proposed by Nishi et al

Frequency dependence of microflows upon acoustic interactions with fluids

Rayleigh surface acoustic waves (SAWs), generated on piezoelectric substrates, can interact with liquids to generate fast streaming flows. Although studied extensively, mainly phenomenologically, the effect of the SAW frequency on streaming in fluids in constrained volumes is not fully understood, resulting in sub-optimal correlations between models and experimental observations. Using microfluidic structures to reproducibly define the fluid volume, we use recent advances modeling the body force generated by SAWs to develop a deeper understanding of the effect of acoustic frequency on the magnitude of streaming flows. We implement this as a new predictive tool using a finite element model of fluid motion to establish optimized conditions for streaming. The model is corroborated experimentally over a range of different acoustic excitation frequencies enabling us to validate a design tool, linking microfluidic channel dimensions with frequencies and streaming efficiencies. We show that in typical microfluidic chambers, the length and height of the chamber are critical in determining the optimum frequency, with smaller geometries requiring higher frequencies

Confinement of surface waves at the air-water interface to control aerosol size and dispersity

The precise control over the size and dispersity of droplets, produced within aerosols, is of great interest across many manufacturing, food, cosmetic, and medical industries. Amongst these applications, the delivery of new classes of high value drugs to the lungs has recently attracted significant attention from pharmaceutical companies. This is commonly achieved through the mechanical excitation of surface waves at the air liquid interface of a parent liquid volume. Previous studies have established a correlation between the wavelength on the surface of liquid and the final aerosol size. In this work, we show that the droplet size distribution of aerosols can be controlled by constraining the liquid inside micron-sized cavities and coupling surface acoustic waves into different volumes of liquid inside micro-grids. In particular, we show that by reducing the characteristic physical confinement size (i.e., either the initial liquid volume or the cavities’ diameters), higher harmonics of capillary waves are revealed with a consequent reduction of both aerosol mean size and dispersity. In doing so, we provide a new method for the generation and fine control of aerosols’ sizes distribution

A one-step procedure to probe the viscoelastic properties of cells by Atomic Force Microscopy

The increasingly recognised importance of viscoelastic properties of cells in pathological conditions requires rapid development of advanced cell microrheology technologies. Here, we present a novel Atomic Force Microscopy (AFM)-microrheology (AFM2) method for measuring the viscoelastic properties in living cells, over a wide range of continuous frequencies (0.005 Hz ~ 200 Hz), from a simple stress-relaxation nanoindentation. Experimental data were directly analysed without the need for pre-conceived viscoelastic models. We show the method had an excellent agreement with conventional oscillatory bulk-rheology measurements in gels, opening a new avenue for viscoelastic characterisation of soft matter using minute quantity of materials (or cells). Using this capability, we investigate the viscoelastic responses of cells in association with cancer cell invasive activity modulated by two important molecular regulators (i.e. mutation of the p53 gene and Rho kinase activity). The analysis of elastic (G′(ω)) and viscous (G″(ω)) moduli of living cells has led to the discovery of a characteristic transitions of the loss tangent (G″(ω)/G′(ω)) in the low frequency range (0.005 Hz ~ 0.1 Hz) that is indicative of the capability for cell restructuring of F-actin network. Our method is ready to be implemented in conventional AFMs, providing a simple yet powerful tool for measuring the viscoelastic properties of living cells

Dynamics of semi-flexible polymer solutions in the highly entangled regime

We present experimental evidence that the effective medium approximation (EMA), developed by D.C. Morse [Phys. Rev. E {\bf 63}, 031502, (2001)], provides the correct scaling law of the macroscopic plateau modulus $G^{0}\propto\rho^{4/3}L^{-1/3}_{p}$ (where $\rho$ is the contour length per unit volume and $L_{p}$ is the persistence length) of semi-flexible polymer solutions, in the highly entangled concentration regime. Competing theories, including a self-consistent binary collision approximation (BCA), have instead predicted $G^{0}\propto\rho^{7/5}L^{-1/5}_{p}$. We have tested both the EMA and BCA scaling predictions using actin filament (F-actin) solutions which permit experimental control of $L_p$ independently of other parameters. A combination of passive video particle tracking microrheology and dynamic light scattering yields independent measurements of the elastic modulus $G$ and $L_{p}$ respectively. Thus we can distinguish between the two proposed laws, in contrast to previous experimental studies, which focus on the (less discriminating) concentration functionality of $G$.Comment: 4 pages, 6 figures, Phys. Rev. Lett. (accepted

i-Rheo: determining the linear viscoelastic moduli of colloidal dispersions from step-stress measurements

We report on the application of a Fourier transform based method, `i-Rheo', to evaluate the linear viscoelastic moduli of hard-sphere colloidal dispersions, both in the fluid and glass states, from a direct analysis of raw step-stress (creep) experimental data. We corroborate the efficacy of i-Rheo by comparing the outputs of creep tests performed on homogenous complex fluids to conventional dynamic frequency sweeps. A similar approach is adopted for a number of colloidal suspensions over a broad range of volume fractions. For these systems, we test the limits of the method by varying the applied stress across the materials' linear and non-linear viscoelastic regimes, and we show that the best results are achieved for stress values close to the upper limit of the materials' linear viscoelastic regime; where the signal-to-noise ratio is at its highest and the non-linear phenomena have not appeared yet. We record that, the range of accessible frequencies is controlled at the higher end by the relative weight between the inertia of the instrument and the elasticity of the complex material under investigation; whereas, the lowest accessible frequency is dictated by the extent of the materials' linear viscoelastic regime. Nonetheless, despite these constrains, we confirm the effectiveness of i-Rheo for gaining valuable information on the materials' linear viscoelastic properties even from creep ringing data, confirming its potency and general validity as an accurate method for determining the material's rheological behaviour for a variety of complex systems

Lipid topology and linear cationic antimicrobial peptides: a novel mechanistic model

The dataset is a dedicated LabVIEW virtual instrument, for the analysis of dye-efflux dynamics. The instrument is capable of automatically extracting the apparent permeability from the leakage of encapsulated fluorescent markers, from within artificial cell systems