Self-assembly of Nanoparticles on Fluid and Elastic Membranes

This dissertation presents studies on self-assembly of nanoparticles adsorbed onto fluid and elastic membranes. It focuses on particles that are at least one order of magnitude larger than the surface thickness, in which case all chemical details of the surface can be ignored in favor of a coarse-grained representation, and the collective behavior of many particles can be analyzed. We use Monte Carlo and molecular dynamics simulations to study the phase behavior of these systems, and its dependence on the mechanical and geometrical properties of the surface, the strength of the particle-surface interaction and the size and the concentration of the nanoparticles. We present scaling laws and accurate free-enegy calculations to understand the occurrence of the phases of interest, and discuss the implications of our results. Chapters 3 and 4 deal with fluid membranes. We show how fluid membranes can mediate linear aggregation of spherical nanoparticles binding to them for a wide range of biologically relevant bending rigidities. This result is in net contrast with the isotropic aggregation of nanoparticles on fluid interfaces or the expected clustering of isotropic insertions in biological membranes. We find that the key to understanding the stability of linear aggregates resides in the interplay between bending and binding energies of the nanoparticles. Furthermore, we demonstrate how linear aggregation can lead to membrane tubulation and determine how tube formation compares with the competing budding process. The development of tubular structures requires less adhesion energy than budding, pointing to a potentially unexplored route of viral infection and nanoparticle internalization in cells. In Chapters 5 - 8, we shift focus to elastic membranes and study self-assembly of nanoparticles mediated by elastic surfaces of different geometries, namely planar, cylindrical and spherical. Again, a variety of linear aggregates are obtained, but their spatial organization can be controlled by changing the stretching rigidity of the elastic membrane, the strength of the particle adhesion, the curvature of the surface, as well as by introducing surface defects. Furthermore, we show how a fully flexible filament binding to a cylindrical elastic membrane may acquire a macroscopic persistence length and a helical conformation. We find that the filaments helical pitch is completely determined by the mechanical properties of the surface, and can be easiliy tuned. Moreover, we study the collapse of unstretchable (thin) hollow nanotube due to the collective behavior of nanoparticles assembling on its surface, resulting in an ordered nanoparticle engulfment inside the collapsed structure. Our hope is that the results presented in this Dissertation will stimulate further experimental studies of the mechanical properties of fluid and cross-linked membranes, in particular the long range correlations arising due to the particle binding

Reaction rate theory for supramolecular kinetics: application to protein aggregation

Probing the reaction mechanisms of supramolecular processes in soft- and biological matter, such as protein aggregation, is inherently challenging. These processes emerge from the simultaneous action of multiple molecular mechanisms, each of which is associated with the rearrangement of a large number of weak bonds, resulting in a complex free energy landscape with many kinetic barriers. Reaction rate measurements of supramolecular processes at different temperatures can offer unprecedented insights into the underlying molecular mechanisms and their thermodynamic properties. However, to be able to interpret such measurements in terms of the underlying microscopic mechanisms, a key challenge is to establish which properties of the complex free energy landscapes are probed by the reaction rate. Here, we present a reaction rate theory for supramolecular kinetics based on Kramers rate theory for diffusive reactions over multiple kinetic barriers, and apply the results to protein aggregation. Using this framework and Monte Carlo simulations, we show that reaction rates for protein aggregation are of the Arrhenius-Eyring type and that the associated activation energies probe only one relevant barrier along the respective free energy landscapes. We apply this advancement to interpret, both in experiments and in coarse-grained computer simulations, reaction rate measurements of amyloid aggregation kinetics in terms of the underlying molecular mechanisms and associated thermodynamic signatures. Our results establish a general platform for probing the mechanisms and energetics of supramolecular phenomena in soft- and biological matter using the framework of chemical kinetics

Curvature variation controls particle aggregation on fluid vesicles

Cellular membranes exhibit a large variety of shapes, strongly coupled to their function. Many biological processes involve dynamic reshaping of membranes, usually mediated by proteins. This interaction works both ways: while proteins influence the membrane shape, the membrane shape affects the interactions between the proteins. To study these membrane-mediated interactions on closed and anisotropically curved membranes, we use colloids adhered to ellipsoidal membrane vesicles as a model system. We find that two particles on a closed system always attract each other, and tend to align with the direction of largest curvature. Multiple particles form arcs, or, at large enough numbers, a complete ring surrounding the vesicle in its equatorial plane. The resulting vesicle shape resembles a snowman. Our results indicate that these physical interactions on membranes with anisotropic shapes can be exploited by cells to drive macromolecules to preferred regions of cellular or intracellular membranes, and utilized to initiate dynamic processes such as cell division. The same principle could be used to find the midplane of an artificial vesicle, as a first step towards dividing it into two equal parts.BN/Timon Idema La

Research data supporting “Melting transition in lipid vesicles functionalised by mobile DNA linkers”

The dataset contains data on aggregation and melting experiments in samples of DNA-functionalised liposomes as described in the paper "Melting transition in lipid vesicles functionalised by mobile DNA linkers” (Soft Matter  12 (37), 7804-7817). The compressed folders contains sub-folders labelled either as “down0_tempXX_sampleY*” or “up0_tempXX_sampleY*”, each containing full resolution epifluorescence microscopy images in tiff format, acquired as described in the paper. Folders labelled a “down” and “up” are relative to experiments performed on cooling and heating respectively. XX indicates the temperature in degrees Celsius at which the images were acquired. The label Y identifies the number of DNA tethers of each kind (N) present on each vesicle, according to the following scheme: Y=1, 2, 5, 10, 20, 50 -> N=3550,1775, 710, 355, 177, 71. Each folder contains 8 tiff images, whose names end with a number from 0 to 7. These correspond to the different fluorescent channels measured as described in the paper. Specifically: 0 -> Excitation: Marina Blue, Emission: Marina Blue 1 -> No Excitation (background) 2 -> Excitation:Cy3, Emission: Cy3 3 -> No Excitation (background) 4 -> Excitation: Cy3, Emission: Cy5 5 -> No Excitation (background) 6 -> Excitation:Cy5, Emission: Cy5 7 -> No Excitation (background) Images acquired with no excitation are used for background subtraction on the previous image in the sequence. The data shown in Figure 2 of the paper are obtained by averaging over three similar datasets. Analysis methods are described in the Methods section of the paper. These data have been used to produce the plots in Fig. 5(b) and Fig 6(b)-(c) of the paper. The data in Fig. 7(b) and Fig. 8(b) are obtained by averaging over 4 datasets.EPSRC [EP/J017566/1

Adsorption Free Energy Predicts Amyloid Protein Nucleation Rates

Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer\u27s and Parkinson\u27s diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physico-chemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here, we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths, but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process

Adsorption free energy predicts amyloid protein nucleation rates.

Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer's and Parkinson's diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physicochemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process

When Law Doesnt Rule: State Capture of the Judiciary, Prosecution, Police in Serbia

The study When the Law Doesn't Rule, by the Open Society European Policy Institute, Transparency Serbia, and the Centre of Investigative Journalism of Serbia, identifies seven ways in which political control is being exerted over the judiciary, prosecution, and police in Serbia, and how systemic weaknesses in the exercise of the rule of law are being exploited. These include limited accountability of judges and prosecutors for ineffectiveness; the appointment of public prosecutors and court presidents on political grounds; an inordinate amount of discretion allowed to law enforcement when making investigation and prosecution decisions; inappropriate and partial briefing of the media; the misuse and manipulation of statistics; direct political influence on law enforcement; and deliberately dysfunctional criminal investigations in politically sensitive cases.The report illustrates these seven administrative and systemic weaknesses through 12 case studies

Steering self-organisation through confinement

Self-organisation is the spontaneous emergence of spatio-temporal structures and patterns from the interaction of smaller individual units. Examples are found across many scales in very different systems and scientific disciplines, from physics, materials science and robotics to biology, geophysics and astronomy. Recent research has highlighted how self-organisation can be both mediated and controlled by confinement. Confinement is an action over a system that limits its units' translational and rotational degrees of freedom, thus also influencing the system's phase space probability density; it can function as either a catalyst or inhibitor of self-organisation. Confinement can then become a means to actively steer the emergence or suppression of collective phenomena in space and time. Here, to provide a common framework and perspective for future research, we examine the role of confinement in the self-organisation of soft-matter systems and identify overarching scientific challenges that need to be addressed to harness its full scientific and technological potential in soft matter and related fields. By drawing analogies with other disciplines, this framework will accelerate a common deeper understanding of self-organisation and trigger the development of innovative strategies to steer it using confinement, with impact on, e.g., the design of smarter materials, tissue engineering for biomedicine and in guiding active matter