Membrane tension determines the geometry of donut-shaped transcellular holes

2021 ◽  
pp. 108128652110258
Author(s):  
Mehdi Torbati ◽  
Ashutosh Agrawal
Keyword(s):  
Plasma Membrane ◽  
Current Model ◽  
Critical Length ◽  
Hole Diameter ◽  
Endothelial Barrier ◽  
Length Scale ◽  
Flexural Stiffness ◽  
Membrane Tension ◽  
Hole Radius ◽  
Universal Relationship

Bacteria and leukocytes employ donut-shaped transcellular holes in plasma membrane to cross the endothelial barrier. How these fused holes are regulated in a double-bilayer system is currently poorly understood. Here we use membrane physics to present a universal relationship that determines the geometry of the donut-shaped holes. Our study reveals that hole radius is determined by plasma membrane tension via a commonly used critical length scale [Formula: see text] defined by flexural stiffness ([Formula: see text]) and in-plane tension ([Formula: see text]). This relationship suggests that the hole diameter increases with a reduction in membrane tension, a finding aligned with the experimental observations but in contrast with the main current model in the literature.

Toughness Governs the Rupture of the Interfacial H-Bond Assemblies at a Critical Length Scale in Hybrid Materials

Langmuir ◽  
2013 ◽  
Vol 29 (25) ◽  
pp. 8154-8163 ◽  
Author(s):  
Navid Sakhavand ◽  
Prakash Muthuramalingam ◽  
Rouzbeh Shahsavari
Keyword(s):  
Hybrid Materials ◽  
Critical Length ◽  
Length Scale

scholarly journals Transport of vesicular stomatitis virus G protein to the cell surface is signal mediated in polarized and nonpolarized cells.

1996 ◽  
Vol 133 (3) ◽  
pp. 543-558 ◽  
Author(s):  
A Müsch ◽  
H Xu ◽  
D Shields ◽  
E Rodriguez-Boulan
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
G Protein ◽  
Vesicular Stomatitis Virus ◽  
Mdck Cells ◽  
Current Model ◽  
Gh3 Cells ◽  
Plasma Membrane Proteins ◽  
Vesicular Release ◽  
Vesicular Stomatitis

Current model propose that in nonpolarized cells, transport of plasma membrane proteins to the surface occurs by default. In contrast, compelling evidence indicates that in polarized epithelial cells, plasma membrane proteins are sorted in the TGN into at least two vectorial routes to apical and basolateral surface domains. Since both apical and basolateral proteins are also normally expressed by both polarized and nonpolarized cells, we explored here whether recently described basolateral sorting signals in the cytoplasmic domain of basolateral proteins are recognized and used for post TGN transport by nonpolarized cells. To this end, we compared the inhibitory effect of basolateral signal peptides on the cytosol-stimulated release of two basolateral and one apical marker in semi-intact fibroblasts (3T3), pituitary (GH3), and epithelial (MDCK) cells. A basolateral signal peptide (VSVGp) corresponding to the 29-amino acid cytoplasmic tail of vesicular stomatitis virus G protein (VSVG) inhibited with identical potency the vesicular release of VSVG from the TGN of all three cell lines. On the other hand, the VSVG peptide did not inhibit the vesicular release of HA in MDCK cells not of two polypeptide hormones (growth hormone and prolactin) in GH3 cells, whereas in 3T3 cells (influenza) hemagglutinin was inhibited, albeit with a 3x lower potency than VSVG. The results support the existence of a basolateral-like, signal-mediated constitutive pathway from TGN to plasma membrane in all three cell types, and suggest that an apical-like pathway may be present in fibroblast. The data support cargo protein involvement, not bulk flow, in the formation of post-TGN vesicles and predict the involvement of distinct cytosolic factors in the assembly of apical and basolateral transport vesicles.

scholarly journals Fracture Mechanics of Human Blood Clots: Measurements of Toughness and Critical Length scales

2021 ◽  
Author(s):  
Shiyu Liu ◽  
Guangyu Bao ◽  
Zhenwei Ma ◽  
Christian Kastrup ◽  
Jianyu Li
Keyword(s):  
Fracture Mechanics ◽  
Whole Blood ◽  
Significant Contribution ◽  
Critical Length ◽  
Length Scale ◽  
Length Scales ◽  
Platelet Poor Plasma ◽  
Lap Shear ◽  
Blood Clots ◽  
Nonlinear Elastic

Blood coagulates to plug vascular damage and stop bleeding, and thus the function of blood clots in hemostasis depends on their resistance against rupture (toughness). Despite the significance, fracture mechanics of blood clots remains largely unexplored, particularly the measurements of toughness and critical length scales governing clot fracture. Here, we study the fracture behavior of human whole blood clots and platelet-poor plasma clots. The fracture energy of whole blood clots and platelet-poor plasma clots determined using modified lap-shear method is 5.90 +- 1.18 J/m2 and 0.96 +- 0.90 J/m2, respectively. We find that the measured toughness is independent of the specimen geometry and loading conditions. These results reveal a significant contribution of blood cells to the clot fracture, as well as the dissipative length scale and nonlinear elastic length scale governing clot fracture.

scholarly journals Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2107-2117 ◽  
Author(s):  
Nicholas S. Tolwinski ◽  
Eric Wieschaus
Keyword(s):  
Drosophila Melanogaster ◽  
Plasma Membrane ◽  
Nuclear Import ◽  
Current Model ◽  
Cellular Distribution ◽  
Nuclear Retention ◽  
Binding Partners ◽  
Wingless Signaling ◽  
Anchoring System ◽  
Import And Export

Drosophila melanogaster Armadillo plays two distinct roles during development. It is a component of adherens junctions, and functions as a transcriptional activator in response to Wingless signaling. In the current model, Wingless signal causes stabilization of cytoplasmic Armadillo allowing it to enter the nucleus where it can activate transcription. However, the mechanism of nuclear import and export remains to be elucidated. In this study, we show that two gain-of-function alleles of Armadillo activate Wingless signaling by different mechanisms. The S10 allele was previously found to localize to the nucleus, where it activates transcription. In contrast, the ΔArm allele localizes to the plasma membrane, and forces endogenous Arm into the nucleus. Therefore, ΔArm is dependent on the presence of a functional endogenous allele of arm to activate transcription. We show that ΔArm may function by titrating Axin protein to the membrane, suggesting that it acts as a cytoplasmic anchor keeping Arm out of the nucleus. In axin mutants, Arm is localized to the nuclei. We find that nuclear retention is dependent on dTCF/Pangolin. This suggests that cellular distribution of Arm is controlled by an anchoring system, where various nuclear and cytoplasmic binding partners determine its localization.

scholarly journals TOR complex 2 (TORC2) signaling and the ESCRT machinery cooperate in the protection of plasma membrane integrity in yeast

2020 ◽  
Vol 295 (34) ◽  
pp. 12028-12044
Author(s):  
Oliver Schmidt ◽  
Yannick Weyer ◽  
Simon Sprenger ◽  
Michael A. Widerin ◽  
Sebastian Eising ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Integrity ◽  
Homeostatic Regulation ◽  
Membrane Tension ◽  
Membrane Remodeling ◽  
Plasma Membrane Integrity ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Evolutionarily Conserved ◽  
Calcineurin Activity

The endosomal sorting complexes required for transport (ESCRT) mediate evolutionarily conserved membrane remodeling processes. Here, we used budding yeast (Saccharomyces cerevisiae) to explore how the ESCRT machinery contributes to plasma membrane (PM) homeostasis. We found that in response to reduced membrane tension and inhibition of TOR complex 2 (TORC2), ESCRT-III/Vps4 assemblies form at the PM and help maintain membrane integrity. In turn, the growth of ESCRT mutants strongly depended on TORC2-mediated homeostatic regulation of sphingolipid (SL) metabolism. This was caused by calcineurin-dependent dephosphorylation of Orm2, a repressor of SL biosynthesis. Calcineurin activity impaired Orm2 export from the endoplasmic reticulum (ER) and thereby hampered its subsequent endosome and Golgi-associated degradation (EGAD). The ensuing accumulation of Orm2 at the ER in ESCRT mutants necessitated TORC2 signaling through its downstream kinase Ypk1, which repressed Orm2 and prevented a detrimental imbalance of SL metabolism. Our findings reveal compensatory cross-talk between the ESCRT machinery, calcineurin/TORC2 signaling, and the EGAD pathway important for the regulation of SL biosynthesis and the maintenance of PM homeostasis.

scholarly journals Quantitative proteomics of MDCK cells identify unrecognized roles of clathrin adaptor AP-1 in polarized distribution of surface proteins

2019 ◽  
pp. 201821076 ◽  
Author(s):  
Paulo S. Caceres ◽  
Diego Gravotta ◽  
Patrick J. Zager ◽  
Noah Dephoure ◽  
Enrique Rodriguez-Boulan
Keyword(s):  
Plasma Membrane ◽  
Isotope Labeling ◽  
Mdck Cells ◽  
Current Model ◽  
Large Population ◽  
Adaptor Proteins ◽  
Surface Proteins ◽  
Experimental Conditions ◽  
Large Populations ◽  
Clathrin Adaptor

The current model of polarized plasma membrane protein sorting in epithelial cells has been largely generated on the basis of experiments characterizing the polarized distribution of a relatively small number of overexpressed model proteins under various experimental conditions. Thus, the possibility exists that alternative roles of various types of sorting machinery may have been underestimated or missed. Here, we utilize domain-selective surface biotinylation combined with stable isotope labeling with amino acids in cell culture (SILAC) and mass spectrometry to quantitatively define large populations of apical and basolateral surface proteins in Madin-Darby canine kidney (MDCK) cells. We identified 313 plasma membrane proteins, of which 38% were apical, 51% were basolateral, and 11% were nonpolar. Silencing of clathrin adaptor proteins (AP) AP-1A, AP-1B, or both caused redistribution of basolateral proteins as expected but also, of a large population of apical proteins. Consistent with their previously reported ability to compensate for one another, the strongest loss of polarity was observed when we silenced AP-1A and AP-1B simultaneously. We found stronger evidence of compensation in the apical pathway compared with the basolateral pathway. Surprisingly, we also found subgroups of proteins that were affected after silencing just one adaptor, indicating previously unrecognized independent roles for AP-1A and AP-1B. While AP-1B silencing mainly affected basolateral polarity, AP-1A silencing seemed to cause comparable loss of apical and basolateral polarity. Our results uncover previously overlooked roles of AP-1 in polarized distribution of apical and basolateral proteins and introduce surface proteomics as a method to examine mechanisms of polarization with a depth not possible until now.

Observations of a Very Large Critical Length Scale in SrTiO3

1988 ◽  
Vol 60 (21) ◽  
pp. 2172-2175 ◽  
Author(s):  
R. J. Nelmes ◽  
P. E. Hatton ◽  
H. Vass
Keyword(s):  
Critical Length ◽  
Length Scale

scholarly journals Critical length scale controls adhesive wear mechanisms

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ramin Aghababaei ◽  
Derek H. Warner ◽  
Jean-Francois Molinari
Keyword(s):  
Wear Mechanisms ◽  
Adhesive Wear ◽  
Critical Length ◽  
Length Scale

scholarly journals Homeostasis of Plasma Membrane Tension Through Surface Area Regulation in Epithelial Cells

2016 ◽  
Vol 110 (3) ◽  
pp. 623a
Author(s):  
Andreas Janshoff ◽  
Bastian Brueckner ◽  
Stefan Nehls
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Surface Area ◽  
Membrane Tension

scholarly journals Reassessing the mechanics of parasite motility and host-cell invasion

2016 ◽  
Vol 214 (5) ◽  
pp. 507-515 ◽  
Author(s):  
Isabelle Tardieux ◽  
Jake Baum
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Cell Invasion ◽  
Motor System ◽  
Current Model ◽  
Cell Movement ◽  
Host Cell Invasion ◽  
Motor Functions ◽  
Apicomplexan Parasites ◽  
Parasite Motility

The capacity to migrate is fundamental to multicellular and single-celled life. Apicomplexan parasites, an ancient protozoan clade that includes malaria parasites (Plasmodium) and Toxoplasma, achieve remarkable speeds of directional cell movement. This rapidity is achieved via a divergent actomyosin motor system, housed within a narrow compartment that lies underneath the length of the parasite plasma membrane. How this motor functions at a mechanistic level during motility and host cell invasion is a matter of debate. Here, we integrate old and new insights toward refining the current model for the function of this motor with the aim of revitalizing interest in the mechanics of how these deadly pathogens move.

Sign in / Sign up

Export Citation Format

Share Document