title: Geometry-induced protein pattern formation.
abstract: Protein patterns are known to adapt to cell shape and serve as spatial templates that choreograph downstream processes like cell polarity or cell division. However, how can pattern-forming proteins sense and respond to the geometry of a cell, and what mechanistic principles underlie pattern formation? Current models invoke mechanisms based on dynamic instabilities arising from nonlinear interactions between proteins but neglect the influence of the spatial geometry itself. Here, we show that patterns can emerge as a direct result of adaptation to cell geometry, in the absence of dynamical instability. We present a generic reaction module that allows protein densities robustly to adapt to the symmetry of the spatial geometry. The key component is an NTPase protein that cycles between nucleotide-dependent membrane-bound and cytosolic states. For elongated cells, we find that the protein dynamics generically leads to a bipolar pattern, which vanishes as the geometry becomes spherically symmetrical. We show that such a reaction module facilitates universal adaptation to cell geometry by sensing the local ratio of membrane area to cytosolic volume. This sensing mechanism is controlled by the membrane affinities of the different states. We apply the theory to explain AtMinD bipolar patterns in [Formula: see text] EcMinDE Escherichia coli. Due to its generic nature, the mechanism could also serve as a hitherto-unrecognized spatial template in many other bacterial systems. Moreover, the robustness of the mechanism enables self-organized optimization of protein patterns by evolutionary processes. Finally, the proposed module can be used to establish geometry-sensitive protein gradients in synthetic biological systems.
authors.affiliation: Arnold Sommerfeld Center for Theoretical Physics, Ludwig-Maximilians-Universität München, D-80333 Munich, Germany; Center for NanoScience, Ludwig-Maximilians-Universität München, D-80333 Munich, Germany; Donders Institute, Radboud University, 6525 EZ Nijmegen, The Netherlands; Department of Biophysics, Radboud University, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Dominik
authors.initials: D
authors.lastname: Thalmeier
authors.affiliation: Arnold Sommerfeld Center for Theoretical Physics, Ludwig-Maximilians-Universität München, D-80333 Munich, Germany; Center for NanoScience, Ludwig-Maximilians-Universität München, D-80333 Munich, Germany;
authors.forename: Jacob
authors.initials: J
authors.lastname: Halatek
authors.affiliation: Arnold Sommerfeld Center for Theoretical Physics, Ludwig-Maximilians-Universität München, D-80333 Munich, Germany; Center for NanoScience, Ludwig-Maximilians-Universität München, D-80333 Munich, Germany; frey@lmu.de.
authors.forename: Erwin
authors.initials: E
authors.lastname: Frey
mesh_terms: D016764:Cell Polarity; D003600:Cytosol / Q000378:metabolism; D008954:Models, Biological; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins
keywords: Min system; cell polarity; geometry sensing; nonlinear dynamics; pattern formation