scholarly journals Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature

2015 ◽  
Vol 17 (2) ◽  
pp. 137-147 ◽  
Author(s):  
Hunter Elliott ◽  
Robert S. Fischer ◽  
Kenneth A. Myers ◽  
Ravi A. Desai ◽  
Lin Gao ◽  
...  
2014 ◽  
Vol 106 (2) ◽  
pp. 13a
Author(s):  
A.R. Fischer ◽  
Hunter Elliot ◽  
Clare Waterman ◽  
Gaudenz Danuser

2015 ◽  
Vol 112 (5) ◽  
pp. 1428-1433 ◽  
Author(s):  
Alexandra Surcel ◽  
Win Pin Ng ◽  
Hoku West-Foyle ◽  
Qingfeng Zhu ◽  
Yixin Ren ◽  
...  

Current approaches to cancer treatment focus on targeting signal transduction pathways. Here, we develop an alternative system for targeting cell mechanics for the discovery of novel therapeutics. We designed a live-cell, high-throughput chemical screen to identify mechanical modulators. We characterized 4-hydroxyacetophenone (4-HAP), which enhances the cortical localization of the mechanoenzyme myosin II, independent of myosin heavy-chain phosphorylation, thus increasing cellular cortical tension. To shift cell mechanics, 4-HAP requires myosin II, including its full power stroke, specifically activating human myosin IIB (MYH10) and human myosin IIC (MYH14), but not human myosin IIA (MYH9). We further demonstrated that invasive pancreatic cancer cells are more deformable than normal pancreatic ductal epithelial cells, a mechanical profile that was partially corrected with 4-HAP, which also decreased the invasion and migration of these cancer cells. Overall, 4-HAP modifies nonmuscle myosin II-based cell mechanics across phylogeny and disease states and provides proof of concept that cell mechanics offer a rich drug target space, allowing for possible corrective modulation of tumor cell behavior.


2002 ◽  
Vol 109 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Christian Nickel ◽  
Thomas Benzing ◽  
Lorenz Sellin ◽  
Peter Gerke ◽  
Anil Karihaloo ◽  
...  

1998 ◽  
Vol 356 ◽  
pp. 149-153 ◽  
Author(s):  
MICHAEL S. LONGUET-HIGGINS

For two-dimensional flow there is a simple relation between the vorticity at a stress-free surface and the surface curvature. In this note the relation is generalized to flow in three dimensions. It is shown that in addition to a component of vorticity perpendicular to the flow there is also a component parallel to the direction of flow. The latter vanishes only at an umbilical point or when the flow is in one of the two principal directions of curvature.


Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 542-551 ◽  
Author(s):  
AA Higazi ◽  
RH Upson ◽  
RL Cohen ◽  
J Manuppello ◽  
J Bognacki ◽  
...  

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.


Immunobiology ◽  
1984 ◽  
Vol 166 (2) ◽  
pp. 111-117
Author(s):  
E. Kownatzki ◽  
Sibylle Uhrich ◽  
Birgit Weil

1978 ◽  
Vol 18 (1) ◽  
pp. 13-23 ◽  
Author(s):  
STEVEN B. OPPENHEIMER

i-Perception ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 204166952090355 ◽  
Author(s):  
Peter U. Tse

Binocular disparity can give rise to the perception of open surfaces or closed curved surfaces (volumes) that appear to vary smoothly across discrete depths. Here I build on my recent papers by providing examples where modally completing surfaces not only fill in from one depth layer’s visible contours to another layer’s visible contours within virtual contours in an analog manner, but where modally completing surface curvature is altered by the interpolation of an abutting object perceived to be connected to or embedded within that modally completing surface. Seemingly minor changes in such an abutting object can flip the interpretation of distal regions, for example, turning a distant edge (where a surface ends) into rim (where a surface bends to occlude itself) or turning an open surface into a closed one. In general, the interpolated modal surface appears to deform, warp, or bend in three-dimensions to accommodate the abutting object. These demonstrations cannot be easily explained by existing models of visual processing or modal completion and drive home the implausibility of localistic accounts of modal or amodal completion that are based, for example, solely on extending contours in space until they meet behind an occluder or in front of “pacmen.” These demonstrations place new constraints on the holistic surface and volume generation processes that construct our experience of a three-dimensional world of surfaces and objects under normal viewing conditions.


2020 ◽  
Vol 31 (20) ◽  
pp. 2234-2248
Author(s):  
Maha Abedrabbo ◽  
Shoshana Ravid

Here we show that Scribble (Scrib), Lethal giant larvae 1 (Lgl1), and myosin II form a complex in vivo and colocalize at the cell leading edge of migrating cells, and this colocalization is interdependent. Scrib and Lgl1 are required for proper cell adhesion, polarity, and migration.


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