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The origin of life is shrouded in mystery, with few surviving clues, obscured by evolutionary competition. Previous reviews have touched on the complementary approaches of top-down and bottom-up synthetic biology to augment our understanding of living systems. Here we point out the synergies between these fields, especially between bottom-up synthetic biology and origin of life research. We explore recent progress made in artificial cell compartmentation in line with the crowded cell, its metabolism, as well as cycles of growth and division, and how those efforts are starting to be combined. Though the complexity of current life is among its most striking characteristics, none of life's essential features require it, and they are unlikely to have emerged thus complex from the beginning. Rather than recovering the one true origin lost in time, current research converges towards reproducing the emergence of minimal life, by teasing out how complexity and evolution may arise from a set of essential components., Comment: 29 pages, 2 figures, 1 table

Non-equilibrium conditions must have been crucial for the assembly of the first informational polymers of early life, but supporting their formation and continuous enrichment in a long-lasting environment. Here, we explore how gas bubbles in water subjected to a thermal gradient, a likely scenario within crustal mafic rocks on the early Earth, drive a complex, continuous enrichment of prebiotic molecules. NRA precursors, monomers, active ribozymes, oligonucleotides and lipids are shown to (1) cycle between dry and wet states, enabling the central step of RNA phosphorylation, (2) accumulate at the gas-water interface to drastically increase ribozymatic activity, (3) condense into hydrogels, (4) form pure crystals and (5) encapsulate into protecting vesicle aggregates that subsequently undergo fission. These effects occur within less than 30 min. The findings unite, in one location, the physical conditions that were crucial for the chemical emergence of biopolymers. They suggest that heated microbubbles could have hosted the first cycles of molecular evolution., Comment: 27 pages, 7 Figures

Scanning fluorescence correlation spectroscopy (SFCS) with a scan path perpendicular to the membrane plane was introduced to measure diffusion and interactions of fluorescent components in free standing biomembranes. Using a confocal laser scanning microscope (CLSM) the open detection volume is moved laterally with kHz frequency through the membrane and the photon events are continuously recorded and stored in a file. While the accessory hardware requirements for a conventional CLSM are minimal, data evaluation can pose a bottleneck. The photon events must be assigned to each scan, in which the maximum signal intensities have to be detected, binned, and aligned between the scans, in order to derive the membrane related intensity fluctuations of one spot. Finally, this time-dependent signal must be correlated and evaluated by well known FCS model functions. Here we provide two platform independent, open source software tools (PyScanFCS and PyCorrFit) that allow to perform all of these steps and to establish perpendicular SFCS in its one- or two-focus as well as its single- or dual-colour modality., Comment: 16 pages, 4 figures

Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms., Comment: 17 pages, 14 figures, review article

The Min proteins from Escherichia coli can self-organize into traveling waves on supported lipid bilayers. In Proc. Natl. Acad. Sci. USA 109, 15283 (2012) we showed that these waves are guided along the boundaries of membrane patches. We introduced an effective two-dimensional model reproducing the observed patterns. In arXiv:1403.5934v1, Jacob Halatek and Erwin Frey contest the ability of our effective two-dimensional model to describe the dynamics of Min proteins on patterned supported lipid bilayers. We thank Halatek and Frey for their interest in our work and for again highlighting the importance of dimensionality and geometry for pattern formation by the Min proteins. Here we reply in detail to the objections by Halatek and Frey and show that (1) our effective two-dimensional model reproduces the observed patterns on isolated patches and that (2) a three-dimensional version of our model produces similar patterns on square patches., Comment: 16 pages, 6 figures, 2 supplementary movies

We address the relationship between membrane microheterogeneity and anomalous subdiffusion in cell membranes by carrying out Monte Carlo simulations of two-component lipid membranes. We find that near-critical fluctuations in the membrane lead to transient subdiffusion, while membrane-cytoskeleton interaction strongly affects phase separation, enhances subdiffusion, and eventually leads to hop diffusion of lipids. Thus, we present a minimum realistic model for membrane rafts showing the features of both microscopic phase separation and subdiffusion., Comment: 21 pages, 5 figures; Supporting Material 5 pages, 1 figure, 1 table

By means of lattice-based Monte Carlo simulations, we address properties of two-component lipid membranes on the experimentally relevant spatial scales of order of a micrometer and time intervals of order of a second, using DMPC/DSPC lipid mixtures as a model system. Our large-scale simulations allowed us to obtain important results previously not reported in simulation studies of lipid membranes. We find that, within a certain range of lipid compositions, the phase transition from the fluid phase to the fluid-gel phase coexistence proceeds via near-critical fluctuations, while for other lipid compositions this phase transition has a quasi-abrupt character. In the presence of near-critical fluctuations, transient subdiffusion of lipid molecules is observed. These features of the system are stable with respect to perturbations in lipid interaction parameters used in our simulations. The line tension characterizing lipid domains in the fluid-gel coexistence region is found to be in the pN range. When approaching the critical point, the line tension, the inverse correlation length of fluid-gel spatial fluctuations, and the corresponding inverse order parameter susceptibility of the membrane vanish. All these results are in agreement with recent experimental findings for model lipid membranes. Our analysis of the domain coarsening dynamics after an abrupt quench of the membrane to the fluid-gel coexistence region reveals that lateral diffusion of lipids plays an important role in the fluid-gel phase separation process., Comment: 45 pages, 15 figures