We report the first 4-component phase diagram for the lipid bilayer mixture, DSPC/DOPC/POPC/chol (distearoylphosphatidylcholine/dioleoylphosphatidylcholine/1-palmitoyl, 2-oleoylphosphatidylcholine/cholesterol). This phase diagram, which has macroscopic Ld + Lo phase domains, clearly shows that all phase boundaries determined for the 3-component mixture containing DOPC transition smoothly into the boundaries for the 3-component mixture containing POPC, which has nanoscopic phase domains of Ld + Lo. Our studies start from two published ternary phase diagrams, and show how these can be combined into a quaternary phase diagram by study of a few hundred samples of intermediate compositions.

In this work we studied memory and irreversible transport phenomena in a nonequilibrium thermodynamically model for genomic transcriptional regulation. Transcriptional regulation possess an extremely complex phenomenology, and it is, of course, of foremost importance in organismal cell development and in the pathogenesis of complex diseases. A better understanding of the way in which these processes occur is mandatory to optimize the construction of gene regulatory networks, but also to connect these networks with multi-scale phenomena (e.g. metabolism, signaling pathways, etc.) under an integrative Systems Biology-like vision. We analyzed three simple mechanisms of genetic stimulation: an instant pulse, a periodic biochemical signal and a saturation process with sigmoidal kinetics and from these we derived the system's thermodynamical response, in the form of, for example, anomalous transcriptional bursts. Transcriptional regulation is an intrinsically stochastic process. There is increasing evidence, for example, of stochastic stabilization of biological clocks and oscillators relative to their classical description based on macroscopic rate equations. Elucidating the effect of randomness on biological oscillation is central to understanding the design principles of robust oscillators, or to the design of synthetic networks. We study the oscillatory instabilities of two model systems that rely on delayed negative feedback to induce oscillation: a single gene auto repressor system, and a dimer negative autoregulation system. We focus on fluctuations of intrinsic origin in the range of low copy number. The bifurcation diagram is obtained for these stochastic models, and shown to differ significantly from that of a macroscopic description that neglects fluctuations. Bifurcation lines remain sharp under fluctuations, but their location is a function of the relative size of the fluctuations. Shifts in the stability threshold of the oscillators can be traced back to the interplay between statistical correlations and delayed feedback. We finally show that there results cannot be captured by weak noise approximations (the diffusion limit), but instead result from strong fluctuations associated with low copy numbers.

No abstract