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Theoretical physicists working at a blackboard collaboration pod in the Beecroft building.
Credit: Jack Hobhouse

Alexander Mietke

Associate Professor of Theoretical Soft Matter and Biophysics

Research theme

  • Biological physics

Sub department

  • Rudolf Peierls Centre for Theoretical Physics

Research groups

  • Condensed Matter Theory
Telephone: 01865 273956
Rudolf Peierls Centre for Theoretical Physics, room 70.26
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  • About
  • Publications

Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early Caenorhabditis elegans development.

eLife 9 (2020) e54930

Authors:

Lokesh G Pimpale, Teije C Middelkoop, Alexander Mietke, Stephan W Grill

Abstract:

Proper positioning of cells is essential for many aspects of development. Daughter cell positions can be specified via orienting the cell division axis during cytokinesis. Rotatory actomyosin flows during division have been implied in specifying and reorienting the cell division axis, but how general such reorientation events are, and how they are controlled, remains unclear. We followed the first nine divisions of Caenorhabditis elegans embryo development and demonstrate that chiral counter-rotating flows arise systematically in early AB lineage, but not in early P/EMS lineage cell divisions. Combining our experiments with thin film active chiral fluid theory we identify a mechanism by which chiral counter-rotating actomyosin flows arise in the AB lineage only, and show that they drive lineage-specific spindle skew and cell reorientation events. In conclusion, our work sheds light on the physical processes that underlie chiral morphogenesis in early development.
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Minimal Model of Cellular Symmetry Breaking.

Physical review letters 123:18 (2019) 188101

Authors:

Alexander Mietke, V Jemseena, K Vijay Kumar, Ivo F Sbalzarini, Frank Jülicher

Abstract:

The cell cortex, a thin film of active material assembled below the cell membrane, plays a key role in cellular symmetry-breaking processes such as cell polarity establishment and cell division. Here, we present a minimal model of the self-organization of the cell cortex that is based on a hydrodynamic theory of curved active surfaces. Active stresses on this surface are regulated by a diffusing molecular species. We show that coupling of the active surface to a passive bulk fluid enables spontaneous polarization and the formation of a contractile ring on the surface via mechanochemical instabilities. We discuss the role of external fields in guiding such pattern formation. Our work reveals that key features of cellular symmetry breaking and cell division can emerge in a minimal model via general dynamic instabilities.
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Attachment of the blastoderm to the vitelline envelope affects gastrulation of insects.

Nature 568:7752 (2019) 395-399

Authors:

Stefan Münster, Akanksha Jain, Alexander Mietke, Anastasios Pavlopoulos, Stephan W Grill, Pavel Tomancak

Abstract:

During gastrulation, physical forces reshape the simple embryonic tissue to form the complex body plans of multicellular organisms1. These forces often cause large-scale asymmetric movements of the embryonic tissue2,3. In many embryos, the gastrulating tissue is surrounded by a rigid protective shell4. Although it is well-recognized that gastrulation movements depend on forces that are generated by tissue-intrinsic contractility5,6, it is not known whether interactions between the tissue and the protective shell provide additional forces that affect gastrulation. Here we show that a particular part of the blastoderm tissue of the red flour beetle (Tribolium castaneum) tightly adheres in a temporally coordinated manner to the vitelline envelope that surrounds the embryo. This attachment generates an additional force that counteracts tissue-intrinsic contractile forces to create asymmetric tissue movements. This localized attachment depends on an αPS2 integrin (inflated), and the knockdown of this integrin leads to a gastrulation phenotype that is consistent with complete loss of attachment. Furthermore, analysis of another integrin (the αPS3 integrin, scab) in the fruit fly (Drosophila melanogaster) suggests that gastrulation in this organism also relies on adhesion between the blastoderm and the vitelline envelope. Our findings reveal a conserved mechanism through which the spatiotemporal pattern of tissue adhesion to the vitelline envelope provides controllable, counteracting forces that shape gastrulation movements in insects.
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Publisher Correction: Attachment of the blastoderm to the vitelline envelope affects gastrulation of insects.

Nature 568:7753 (2019) E14

Authors:

Stefan Münster, Akanksha Jain, Alexander Mietke, Anastasios Pavlopoulos, Stephan W Grill, Pavel Tomancak

Abstract:

In this Letter, the sentence starting: 'For instance, Tribolium and Drosophila inflated are direct targets of the mesoderm…' has been corrected online; see accompanying Amendment.
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Self-organized shape dynamics of active surfaces.

Proceedings of the National Academy of Sciences of the United States of America 116:1 (2019) 29-34

Authors:

Alexander Mietke, Frank Jülicher, Ivo F Sbalzarini

Abstract:

Mechanochemical processes in thin biological structures, such as the cellular cortex or epithelial sheets, play a key role during the morphogenesis of cells and tissues. In particular, they are responsible for the dynamical organization of active stresses that lead to flows and deformations of the material. Consequently, advective transport redistributes force-generating molecules and thereby contributes to a complex mechanochemical feedback loop. It has been shown in fixed geometries that this mechanism enables patterning, but the interplay of these processes with shape changes of the material remains to be explored. In this work, we study the fully self-organized shape dynamics using the theory of active fluids on deforming surfaces and develop a numerical approach to solve the corresponding force and torque balance equations. We describe the spontaneous generation of nontrivial surface shapes, shape oscillations, and directed surface flows that resemble peristaltic waves from self-organized, mechanochemical processes on the deforming surface. Our approach provides opportunities to explore the dynamics of self-organized active surfaces and can help to understand the role of shape as an integral element of the mechanochemical organization of morphogenetic processes.
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