scholarly journals Effect of Post-mortem Interval and Perfusion on the Biophysical Properties of ex vivo Liver Tissue Investigated Longitudinally by MRE and DWI

2021 ◽  
Vol 12 ◽  
Author(s):  
Karolina Garczyńska ◽  
Heiko Tzschätzsch ◽  
Sanam Assili ◽  
Anja A. Kühl ◽  
Akvile Häckel ◽  
...  
Keyword(s):  
Cell Wall ◽  
Shear Wave ◽  
Liver Tissue ◽  
Cell Shape ◽  
Ex Vivo ◽  
Cell Wall Integrity ◽  
Post Mortem ◽  
Biophysical Properties ◽  
Water Diffusivity ◽  
Tissue Degradation

Structural changes of soft tissues on the cellular level can be characterized by histopathology, but not longitudinally in the same tissue. Alterations of cellular structures and tissue matrix are associated with changes in biophysical properties which can be monitored longitudinally by quantitative diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE). In this work, DWI and MRE examinations were performed in a 0.5-Tesla compact scanner to investigate longitudinal changes in water diffusivity, stiffness and viscosity of ex-vivo rat livers for up to 20 h post-mortem (pm). The effect of blood on biophysical parameters was examined in 13 non-perfused livers (containing blood, NPLs) and 14 perfused livers (blood washed out, PLs). Changes in cell shape, cell packing and cell wall integrity were characterized histologically. In all acquisitions, NPLs presented with higher shear-wave speed (c), higher shear-wave penetration rate (a) and smaller apparent-diffusion-coefficients (ADCs) than PL. Time-resolved analysis revealed three distinct phases: (i) an initial phase (up to 2 h pm) with markedly increased c and a and reduced ADCs; (ii) an extended phase with relatively stable values; and (iii) a degradation phase characterized by significant increases in a (10 h pm in NPLs and PLs) and ADCs (10 h pm in NPLs, 13 h pm in PLs). Histology revealed changes in cell shape and packing along with decreased cell wall integrity, indicating tissue degradation in NPLs and PLs 10 h pm. Taken together, our results demonstrate that the biophysical properties of fresh liver tissue rapidly change within 2 h pm, which seems to be an effect of both cytotoxic edema and vascular blood content. Several hours later, disruption of cell walls resulted in higher water diffusivity and wave penetration. These results reveal the individual contributions of vascular components and cellular integrity to liver elastography and provide a biophysical, imaging-based fingerprint of liver tissue degradation.

scholarly journals Coordinating cell polarization and morphogenesis through mechanical feedback

2020 ◽  
Author(s):  
Samhita P. Banavar ◽  
Michael Trogdon ◽  
Brian Drawert ◽  
Tau-Mu Yi ◽  
Linda R. Petzold ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Shape ◽  
Cell Polarization ◽  
Cell Wall Integrity ◽  
Coarse Grained ◽  
Cellular Processes ◽  
Cell Wall Integrity Pathway ◽  
Molecular Machinery ◽  
Mating Projection ◽  
Mechanical Feedback

AbstractMany cellular processes require cell polarization to be maintained as the cell changes shape, grows or moves. Without feedback mechanisms relaying information about cell shape to the polarity molecular machinery, the coordination between cell polarization and morphogenesis, movement or growth would not be possible. Here we theoretically and computationally study the role of a genetically-encoded mechanical feedback (in the Cell Wall Integrity Pathway) as a potential coordination mechanism between cell morphogenesis and polarity during budding yeast mating projection growth. We developed a coarse-grained continuum description of the coupled dynamics of cell polarization and morphogenesis as well as 3D stochastic simulations of the molecular polarization machinery in the evolving cell shape. Both theoretical approaches show that in the absence of mechanical feedback (or in the presence of weak feedback), cell polarity cannot be maintained at the projection tip during growth, with the polarization cap wandering off the projection tip, arresting morphogenesis. In contrast, for mechanical feedback strengths above a threshold, cells can robustly maintain cell polarization at the tip and simultaneously sustain mating projection growth. These results indicate that the mechanical feedback encoded in the Cell Wall Integrity pathway can provide important positional information to the molecular machinery in the cell, thereby enabling the coordination of cell polarization and morphogenesis.Author summaryCell migration, morphogenesis and secretion are among the vast number of cellular processes that require cells to define a preferred spatial direction to perform essential tasks. This is achieved by setting an intracellular molecular gradient that polarizes the cell. While the molecular players involved in cell polarization and some of the mechanisms that cells use to establish such molecular gradients are known, it remains unclear how cells maintain polarization as they dramatically change shape during morphogenesis, migration, etc. Here we identify a potential feedback control mechanism, encoded genetically in cells, that provides the molecular polarization machinery with the necessary information about cell geometry to maintain cell polarization during cell shape changes.

scholarly journals A 60-Kilodalton Immunodominant Glycoprotein Is Essential for Cell Wall Integrity and the Maintenance of Cell Shape in Streptococcus mutans

2002 ◽  
Vol 70 (3) ◽  
pp. 1665-1665
Author(s):  
Jean-San Chia ◽  
Lan Yi Chang ◽  
Chia-Tung Shun ◽  
Ying-Ying Chang ◽  
Yeou-Guang Tsay ◽  
...  
Keyword(s):  
Cell Wall ◽  
Streptococcus Mutans ◽  
Cell Shape ◽  
Cell Wall Integrity

scholarly journals Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe.

1997 ◽  
Vol 17 (7) ◽  
pp. 3508-3519 ◽  
Author(s):  
A S Sengar ◽  
N A Markley ◽  
N J Marini ◽  
D Young
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Cell Growth ◽  
Stationary Phase ◽  
Cell Morphology ◽  
Cell Shape ◽  
Catalytic Domain ◽  
Salt Resistance ◽  
Cell Wall Integrity ◽  
Phase Arrest

We have identified a Schizosaccharomyces pombe gene, mkh1, that encodes a MEK kinase (MEKK) homolog. The coding region of mkh1 is contained within a single exon encoding a 1,116-amino-acid protein. The putative catalytic domain of Mkh1 is 54% identical to the catalytic domain of S. cerevisiae Bck1, the most closely related protein. Deletion of mkh1 did not significantly affect cell growth or division under standard conditions. However, mkh1delta cell growth was inhibited by high KCl or NaCl concentrations. mkh1delta cells required a longer time to reenter the cell cycle after prolonged stationary-phase arrest. Also, mkh1delta cells exhibited a round cell shape, while overexpression of Mkh1 resulted in an elongated cell shape. mkh1delta cells exhibited a more dramatic phenotype when grown in nutrient-limiting conditions at high temperature or in hyperosmotic medium. In such conditions, completion of cytokinesis was inhibited, resulting in the growth of pseudohyphal filaments with multiple septa and nuclei. Also, mkh1delta cells were hypersensitive to beta-glucanase treatment. Together these results suggest that Mkh1 regulates cell morphology, cell wall integrity, salt resistance, cell cycle reentry from stationary-phase arrest, and filamentous growth in response to stress. These phenotypes are essentially identical to those exhibited by cells lacking Pmk1/Spm1, a recently identified mitogen-activated protein kinase. Our evidence suggests that Pmk1/Spm1 acts downstream from Mkh1 in a common pathway. Our results also suggest that Mkh1 and Pck2 act independently to maintain cell wall integrity, cell morphology, and salt resistance but act in opposition to regulate filamentous growth.

scholarly journals Coordinating cell polarization and morphogenesis through mechanical feedback

2021 ◽  
Vol 17 (1) ◽  
pp. e1007971
Author(s):  
Samhita P. Banavar ◽  
Michael Trogdon ◽  
Brian Drawert ◽  
Tau-Mu Yi ◽  
Linda R. Petzold ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Shape ◽  
Cell Polarization ◽  
Cell Wall Integrity ◽  
Coarse Grained ◽  
Theoretical Approaches ◽  
Cell Wall Integrity Pathway ◽  
Molecular Machinery ◽  
Mating Projection ◽  
Mechanical Feedback

Many cellular processes require cell polarization to be maintained as the cell changes shape, grows or moves. Without feedback mechanisms relaying information about cell shape to the polarity molecular machinery, the coordination between cell polarization and morphogenesis, movement or growth would not be possible. Here we theoretically and computationally study the role of a genetically-encoded mechanical feedback (in the Cell Wall Integrity pathway) as a potential coordination mechanism between cell morphogenesis and polarity during budding yeast mating projection growth. We developed a coarse-grained continuum description of the coupled dynamics of cell polarization and morphogenesis as well as 3D stochastic simulations of the molecular polarization machinery in the evolving cell shape. Both theoretical approaches show that in the absence of mechanical feedback (or in the presence of weak feedback), cell polarity cannot be maintained at the projection tip during growth, with the polarization cap wandering off the projection tip, arresting morphogenesis. In contrast, for mechanical feedback strengths above a threshold, cells can robustly maintain cell polarization at the tip and simultaneously sustain mating projection growth. These results indicate that the mechanical feedback encoded in the Cell Wall Integrity pathway can provide important positional information to the molecular machinery in the cell, thereby enabling the coordination of cell polarization and morphogenesis.

The Regulatory Function of the Molecular Chaperone Hsp90 in the Cell Wall Integrity of Pathogenic Fungi

2018 ◽  
Vol 16 (1) ◽  
pp. 44-53
Author(s):  
Marina Campos Rocha ◽  
Camilla Alves Santos ◽  
Iran Malavazi
Keyword(s):  
Cell Wall ◽  
Antifungal Therapy ◽  
Molecular Chaperone ◽  
Regulatory Protein ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Cell Wall Integrity ◽  
Regulatory Function ◽  
Loss Of Function ◽  
Hsp90 Inhibition

Different signaling cascades including the Cell Wall Integrity (CWI), the High Osmolarity Glycerol (HOG) and the Ca2+/calcineurin pathways control the cell wall biosynthesis and remodeling in fungi. Pathogenic fungi, such as Aspergillus fumigatus and Candida albicans, greatly rely on these signaling circuits to cope with different sources of stress, including the cell wall stress evoked by antifungal drugs and the host’s response during infection. Hsp90 has been proposed as an important regulatory protein and an attractive target for antifungal therapy since it stabilizes major effector proteins that act in the CWI, HOG and Ca2+/calcineurin pathways. Data from the human pathogen C. albicans have provided solid evidence that loss-of-function of Hsp90 impairs the evolution of resistance to azoles and echinocandin drugs. In A. fumigatus, Hsp90 is also required for cell wall integrity maintenance, reinforcing a coordinated function of the CWI pathway and this essential molecular chaperone. In this review, we focus on the current information about how Hsp90 impacts the aforementioned signaling pathways and consequently the homeostasis and maintenance of the cell wall, highlighting this cellular event as a key mechanism underlying antifungal therapy based on Hsp90 inhibition.

scholarly journals Probing bacterial cell wall growth by tracing wall-anchored protein complexes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi-Jen Sun ◽  
Fan Bai ◽  
An-Chi Luo ◽  
Xiang-Yu Zhuang ◽  
Tsai-Shun Lin ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Shape ◽  
Bernoulli Shift ◽  
Protein Complexes ◽  
Axial Direction ◽  
Cell Wall Growth ◽  
Flagellar Motors ◽  
Shift Map ◽  
Dynamic Assembly ◽  
Wall Growth

AbstractThe dynamic assembly of the cell wall is key to the maintenance of cell shape during bacterial growth. Here, we present a method for the analysis of Escherichia coli cell wall growth at high spatial and temporal resolution, which is achieved by tracing the movement of fluorescently labeled cell wall-anchored flagellar motors. Using this method, we clearly identify the active and inert zones of cell wall growth during bacterial elongation. Within the active zone, the insertion of newly synthesized peptidoglycan occurs homogeneously in the axial direction without twisting of the cell body. Based on the measured parameters, we formulate a Bernoulli shift map model to predict the partitioning of cell wall-anchored proteins following cell division.

scholarly journals Yeast Nap1-Binding Protein Nbp2p Is Required for Mitotic Growth at High Temperatures and for Cell Wall Integrity

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 517-529
Author(s):  
Kentaro Ohkuni ◽  
Asuko Okuda ◽  
Akihiko Kikuchi
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
High Temperature ◽  
High Temperatures ◽  
Hybrid System ◽  
Mapk Pathway ◽  
Binding Protein ◽  
Cell Wall Integrity ◽  
Calcofluor White ◽  
Two Hybrid

AbstractNbp2p is a Nap1-binding protein in Saccharomyces cerevisiae identified by its interaction with Nap1 by a two-hybrid system. NBP2 encodes a novel protein consisting of 236 amino acids with a Src homology 3 (SH3) domain. We showed that NBP2 functions to promote mitotic cell growth at high temperatures and cell wall integrity. Loss of Nbp2 results in cell death at high temperatures and in sensitivity to calcofluor white. Cell death at high temperature is thought not to be due to a weakened cell wall. Additionally, we have isolated several type-2C serine threonine protein phosphatases (PTCs) as multicopy suppressors and MAP kinase-kinase (MAPKK), related to the yeast PKC MAPK pathway, as deletion suppressors of the nbp2Δ mutant. Screening for deletion suppressors is a new genetic approach to identify and characterize additional proteins in the Nbp2-dependent pathway. Genetic analyses suggested that Ptc1, which interacts with Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is indispensable when Nbp2 is deleted at high temperature.

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