Phase behaviour of colloidal assemblies on 2D corrugated substrates

We investigate - with Monte Carlo computer simulations - the phase behaviour of dimeric colloidal molecules on periodic substrates with square symmetry. The molecules are formed in a two-dimensional suspension of like charged colloids subject to periodic external confinement, which can be experimentally realized by optical methods. We study the evolution of positional and orientational order by varying the temperature across the melting transition. We propose and evaluate appropriate order parameters as well as the specific heat capacity and show that the decay of positional correlations belongs to a class of crossover transitions while the orientational melting is a second-order phase transition.Comment: 13 pages, 9 figures, accepted in J. Phys.: Condens. Matte

Multivalent binding and selectivity in cell targeting, molecular recognition and receptor activation

MULTIVALENT BINDING AND SELECTIVITY IN CELL TARGETING, MOLECULAR RECOGNITION AND RECEPTOR ACTIVATION Jure Dobnikar, Institute of Physics, Chinese Academy of Sciences, Beijing, Chin ; Department of Chemistry, University of Cambridge, UK ; School of physical sciences, University of Chinese Academy of Sciences One of the key challenges in nano-science is to design nanoparticles that can recognize and target specific objects. One such example are ligand-coated nanoparticles binding to surfaces covered with receptors forming bonds with the ligands. The requirement of many applications is that the particles bind selectively to surfaces with receptors either above a threshold concentration or in a specific geometric arrangement. Such nanoparticles would enable precise functioning of nano machines, as well as selective targeting of cells in drug delivery. Similarly, many biological processes rely on chemical activation based on (macro-) molecular recognition. Also in this case, the receptors need to selectively bind to specific molecules to get activated. In recent years, it has been shown that super-selectivity can only be achieved with multiple weak reversible bonds where many ligands simultaneously bind to the surface receptors. Only in such systems, the fraction of bound particles varies sharply with the receptor concentration and nano-particles can be designed such that they approach the on-off binding behaviour required for super- selective targeting. I will report on our recent work on physics of multivalent binding and specifically address targeting cancer cells, molecular recognition and multivalent receptor activation by DNA-peptide complexes in the immune system. Publications: [1] N.W. Schmidt, F. Jin, R. Lande, T. Curk, W. Xian, L. Frasca, D. Frenkel, J. Dobnikar, M. Gilliet, G.C.L. Wong, Antimicrobial-peptide-DNA complexes amplify TLR9 activation via liquid-crystalline ordering, Nature Materials 14, 696 (2015) [2] T. Curk, J. Dobnikar, D. Frenkel, Rational design of molecularly imprinted polymers, Soft Matter 12, 35 (2016) [3] T. Curk, J. Dobnikar, and D. Frenkel, Optimal multivalent targeting of mem- branes with many distinct receptors, to appear in PNAS (2017

Efficient simulations of charged colloidal dispersions: A density functional approach

A numerical method is presented for first-principle simulations of charged colloidal dispersions in electrolyte solutions. Utilizing a smoothed profile for colloid-solvent boundaries, efficient mesoscopic simulations are enabled for modeling dispersions of many colloidal particles exhibiting many-body electrostatic interactions. The validity of the method was examined for simple colloid geometries, and the efficiency was demonstrated by calculating stable structures of two-dimensional dispersions, which resulted in the formation of colloidal crystals.Comment: 6 pages, 4 figure

A genome-wide, single-cell analysis of vascular smooth muscle cell plasticity

Vascular smooth muscle cells (VSMCs) possess a remarkable capacity to change phenotype in response to injury or inflammation. In healthy arteries, VSMCs exist in a contractile state, but upon vascular inflammation or injury, they can switch into an activated state, in which they downregulate the contractile differentiation markers and show increased migration, proliferation and secretion of proinflammatory cytokines. This process is termed phenotypic switching and can lead to VSMC accumulation within atherosclerotic plaques. Previous observations of clonal expansion of a small number of VSMCs in atherosclerosis suggested that VSMCs were functionally heterogeneous. I hypothesised that functional heterogeneity of VSMCs in disease may originate from VSMC heterogeneity in healthy arteries. In the first part of this thesis I explored the regional heterogeneity of VSMCs originating from different parts of the mouse aorta, as well as heterogeneity of VSMCs within a vascular bed using single-cell and bulk RNA sequencing. VSMCs originating from the atherosclerosis-prone aortic arch and atherosclerosis-resistant descending thoracic aorta were found to have distinct transcriptional signatures at the single-cell level. Additionally, several disease-relevant genes were observed to be heterogeneously expressed within both vascular beds. In the second chapter I identified and characterised a rare subset of VSMCs expressing Stem cell antigen 1 (SCA1). Single-cell RNA-seq was combined with VSMC-specific lineage tracing to profile gene expression in individual VSMCs from healthy mouse arteries and to compare SCA1-expressing VSMCs to other cells. SCA1-positive VSMCs were heterogeneous, with many of them expressing low levels of contractile VSMC markers. Additionally, a subset of SCA1-positive VSMCs in healthy arteries expressed transcriptional signatures characteristic of activated VSMCs involved in phenotypic switching. In the third chapter I investigated the involvement of SCA1-positive VSMCs in phenotypic switching. SCA1 upregulation was found to mark the process of VSMC phenotypic switching following in vitro culture and in vivo vascular injury. Single-cell RNA-seq profiling of VSMCs in atherosclerosis and following vascular injury showed that Ly6a/Sca1-expressing VSMCs were present and expressed transcriptional signatures similar to activated SCA1-positive cells observed in healthy arteries. Overall the results presented in this thesis highlight the heterogeneous nature of VSMCs in healthy arteries, both regionally and within a vascular bed. I identified a rare subset of SCA1-positive VSMCs with activated transcriptional signatures in healthy arteries. I hypothesised that SCA1-positive VSMCs may be responsible for clonal expansion of VSMCs in atherosclerosis, which would have clinical implications for earlier detection and specific targeting of expanding VSMCs in atherosclerosis in the future. In support of this hypothesis I have shown that Ly6a/Sca1 is upregulated in model systems of VSMC phenotypic switching and that transcriptional signatures of Ly6a/Sca1-expressing VSMCs in mouse atherosclerosis and vascular injury resemble those of healthy activated SCA1-positive VSMCs.BBSRC DTP studentshi

Poisson -- Boltzmann Brownian Dynamics of Charged Colloids in Suspension

We describe a method to simulate the dynamics of charged colloidal particles suspended in a liquid containing dissociated ions and salt ions. Regimes of prime current interest are those of large volume fraction of colloids, highly charged particles and low salt concentrations. A description which is tractable under these conditions is obtained by treating the small dissociated and salt ions as continuous fields, while keeping the colloidal macroions as discrete particles. For each spatial configuration of the macroions, the electrostatic potential arising from all charges in the system is determined by solving the nonlinear Poisson--Boltzmann equation. From the electrostatic potential, the forces acting on the macroions are calculated and used in a Brownian dynamics simulation to obtain the motion of the latter. The method is validated by comparison to known results in a parameter regime where the effective interaction between the macroions is of a pairwise Yukawa form

Observation of condensed phases of quasi-planar core-softened colloids

We experimentally study the condensed phases of repelling core-softened spheres in two dimensions. The dipolar pair repulsion between superparamagnetic spheres trapped in a thin cell is induced by a transverse magnetic field and softened by suitably adjusting the cell thickness. We scan a broad density range and we materialize a large part of the theoretically predicted phases in systems of core-softened particles, including expanded and close-packed hexagonal, square, chain-like, stripe/labyrinthine, and honeycomb phase. Further insight into their structure is provided by Monte Carlo simulations