A colloidal approach to eye lens protein mixtures:relevance for cataract formation

A broad and constantly growing class of diseases, such as Alzheimer's disease, sickle-cell or cataract, involves protein association phenomena as an essential aspect. The common denominator of all the members of this class of molecular condensation diseases is an attractive energy of interaction between specific biologic molecules which produces condensation into dense, frequently insoluble mesoscopic phases. Understanding interprotein interactions is essential since it is the subtle interplay between interprotein attraction, repulsion and solution entropy that leads to the condensed protein phases. Among these diseases, cataract is the world's leading cause of blindness and effective prevention or non-surgical cure are still lacking. The loss of transparency of the eye lens found in cataract originates from the alteration of the spatial distribution of the lens crystallin proteins. Biological studies of the chaperone properties of crystallins have given valuable information about their aggregation in diluted environment. However, since the crystallins are present at high concentration in the eye lens cells, it is crucial to complement these studies with investigations at physiological concentrations where emergent mixture properties, like phase transitions, are expected. The eye lens cytoplasm contains a solution of mainly three classes of water soluble proteins, called α-, β- and γ-crystallin. In this thesis we develop a coarse-grained model for binary mixtures of α- and γ-crystallin proteins. By analyzing our numerical results in conjunction with experimental neutron scattering data, the interactions between the proteins are modeled. We demonstrate that transparency of the eye lens is greatly enhanced by a weak, short-range attraction between α- and γ-crystallin. Provided it is not too strong, such mutual attraction considerably decreases the critical temperature and the corresponding opacity due to light scattering, and it is consequently essential for eye lens transparency. The phase diagram of the binary α-γ model mixture is then investigated via thermodynamic perturbation theory. The instability boundary of the crystallin mixtures is found to depend on the α-γ attraction in a manner that is both extremely sensitive and non-monotonic, in excellent agreement with the experimental and numerical results. Moreover, the composition of the coexisting phases depends strongly on the strength of the α-γ interaction. In light of the tie lines determination it appears that a decrease of the binding affinity of α and γ-crystallins with ageing involves small energy changes in the attraction between the crystallins and can produce sufficient inhomogeneities to lead to the opacification of the lens. The colloidal approach developed in this thesis could be applied in the future to study other mixtures of crystallin proteins and provide new insights into their interactions and thermodynamic stability when combined with scattering experiments and cloud point measurements

Scaling laws for jets of single cavitation bubbles

Fast liquid jets, called micro-jets, are produced within cavitation bubbles experiencing an aspherical collapse. Here we review micro-jets of different origins, scales and appearances, and propose a unified framework to describe their dynamics by using an anisotropy parameter $\zeta$, representing a dimensionless measure of the liquid momentum at the collapse point (Kelvin impulse). This parameter is rigorously defined for various jet drivers, including gravity and nearby boundaries. Combining theoretical considerations with hundreds of high-speed visualisations of bubbles collapsing near a rigid surface, near a free surface or in variable gravity, we classify the jets into three distinct regimes: weak, intermediate and strong. Weak jets ($\zeta<10^{-3}$) hardly pierce the bubble, but remain within it throughout the collapse and rebound. Intermediate jets ($10^{-3}<\zeta<0.1$) pierce the opposite bubble wall close to the last collapse phase and clearly emerge during the rebound. Strong jets ($\zeta>0.1$) pierce the bubble early during the collapse. The dynamics of the jets is analysed through key observables, such as the jet impact time, jet speed, bubble displacement, bubble volume at jet impact and vapour-jet volume. We find that, upon normalising these observables to dimensionless jet parameters, they all reduce to straightforward functions of $\zeta$, which we can reproduce numerically using potential flow theory. An interesting consequence of this result is that a measurement of a single observable, such as the bubble displacement, suffices to estimate any other parameter, such as the jet speed. Remarkably, the dimensionless parameters of intermediate and weak jets only depend on $\zeta$, not on the jet driver. In the same regime, the jet parameters are found to be well approximated by power-laws of $\zeta$, which we explain through analytical arguments

Techniques for Generating Centimetric Drops in Microgravity and Application to Cavitation Studies

This paper describes the techniques and physical parameters used to produce stable centimetric water drops in microgravity, and to study single cavitation bubbles inside such drops (Parabolic Flight Campaigns, European Space Agency ESA). While the main scientific results have been presented in a previous paper, we shall herein provide the necessary technical background, with potential applications to other experiments. First, we present an original method to produce and capture large stable drops in microgravity. This technique succeeded in generating quasi-spherical water drops with volumes up to 8 ml, despite the residual g-jitter. We find that the equilibrium of the drops is essentially dictated by the ratio between the drop volume and the contact surface used to capture the drop, and formulate a simple stability criterion. In a second part, we present a setup for creating and studying single cavitation bubbles inside those drops. In addition, we analyze the influence of the bubble size and position on the drop behaviour after collapse, i.e. jets and surface perturbations

Shock waves from non-spherical cavitation bubbles

We present detailed observations of the shock waves emitted at the collapse of single cavitation bubbles using simultaneous time-resolved shadowgraphy and hydrophone pressure measurements. The geometry of the bubbles is systematically varied from spherical to very non-spherical by decreasing their distance to a free or rigid surface or by modulating the gravity-induced pressure gradient aboard parabolic flights. The non-spherical collapse produces multiple shocks that are clearly associated with different processes, such as the jet impact and the individual collapses of the distinct bubble segments. For bubbles collapsing near a free surface, the energy and timing of each shock are measured separately as a function of the anisotropy parameter $\zeta$, which represents the dimensionless equivalent of the Kelvin impulse. For a given source of bubble deformation (free surface, rigid surface or gravity), the normalized shock energy depends only on $\zeta$, irrespective of the bubble radius $R_{0}$ and driving pressure $\Delta p$. Based on this finding, we develop a predictive framework for the peak pressure and energy of shock waves from non-spherical bubble collapses. Combining statistical analysis of the experimental data with theoretical derivations, we find that the shock peak pressures can be estimated as jet impact-induced hammer pressures, expressed as $p_{h} = 0.45\left(\rho c^{2}\Delta p\right)^{1/2} \zeta^{-1}$ at $\zeta > 10^{-3}$. The same approach is found to explain the shock energy quenching as a function of $\zeta^{-2/3}$.Comment: Accepted for publication in Physical Review Fluid

The Quest for the Most Spherical Bubble

We describe a recently realized experiment producing the most spherical cavitation bubbles today. The bubbles grow inside a liquid from a point-plasma generated by a nanosecond laser pulse. Unlike in previous studies, the laser is focussed by a parabolic mirror, resulting in a plasma of unprecedented symmetry. The ensuing bubbles are sufficiently spherical that the hydrostatic pressure gradient caused by gravity becomes the dominant source of asymmetry in the collapse and rebound of the cavitation bubbles. To avoid this natural source of asymmetry, the whole experiment is therefore performed in microgravity conditions (ESA, 53rd and 56th parabolic flight campaign). Cavitation bubbles were observed in microgravity (~0g), where their collapse and rebound remain spherical, and in normal gravity (1g) to hyper-gravity (1.8g), where a gravity-driven jet appears. Here, we describe the experimental setup and technical results, and overview the science data. A selection of high-quality shadowgraphy movies and time-resolved pressure data is published online.Comment: 18 pages, 14 figures, 1 tabl

Techniques for generating centimetric drops in microgravity and application to cavitation studies

This paper describes the techniques and physical parameters used to produce stable centimetric water drops in microgravity, and to study single cavitation bubbles inside such drops (Parabolic Flight Campaigns, European Space Agency ESA). While the main scientific results have been presented in a previous paper, we shall herein provide the necessary technical background, with potential applications to other experiments. First, we present an original method to produce and capture large stable drops in microgravity. This technique succeeded in generating quasi-spherical water drops with volumes up to 8ml, despite the residual g-jitter. We find that the equilibrium of the drops is essentially dictated by the ratio between the drop volume and the contact surface used to capture the drop, and formulate a simple stability criterion. In a second part, we present a setup for creating and studying single cavitation bubbles inside those drops. In addition, we analyze the influence of the bubble size and position on the drop behaviour after collapse, i.e., jets and surface perturbation

Confined Shocks inside Isolated Liquid Volumes -- A New Path of Erosion?

The unique confinement of shock waves inside isolated liquid volumes amplifies the density of shock-liquid interactions. We investigate this universal principle through an interdisciplinary study of shock-induced cavitation inside liquid volumes, isolated in 2 and 3 dimensions. By combining high-speed visualizations of ideal water drops realized in microgravity with smoothed particle simulations we evidence strong shock-induced cavitation at the focus of the confined shocks. We extend this analysis to ground-observations of jets and drops using an analytic model, and argue that cavitation caused by trapped shocks offers a distinct mechanism of erosion in high-speed impacts (>100 m/s).Comment: 4 page letter, 4 figure

Microgravity Experiment: Cavitation Studies Inside Water Drops

Poster session on microgravity experiments 2006

Direct effects of gravity on cavitation bubble collapse

We propose an experiment for studying the final stages of collapse of a single laser generated cavitation bubble in microgravity. Unlike previous investigations, the goal of the study is to examine the direct effects of gravity on the cavity collapse. In this paper we present ground-based research on these effects and outline a microgravity experiment destined for ESA Microgravity Research Campaign. The proposed experiment uses a focused laser to generate a highly spherical bubble in an extended water volume without disturbing the liquid and measures bubble rebound and shockwave intensity. Buoyancy forces being proportional to bubble volume, smaller bubbles are the least disturbed. Results show that as bubble size decreases, the part of bubble energy transformed into a shockwave increases, to the detriment of the rebound bubble and liquid jets