Mechanical competition alters the cellular interpretation of an endogenous genetic program

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
Sourabh Bhide ◽  
Denisa Gombalova ◽  
Gregor Mönke ◽  
Johannes Stegmaier ◽  
Valentyna Zinchenko ◽  
...  
Keyword(s):  
Genetic Program ◽  
Cell Behavior ◽  
Mechanical Stimuli ◽  
Apical Constriction ◽  
Actin Reorganization ◽  
Ductile Materials ◽  
Nonlinear Mechanical ◽  
A Cell ◽  
Contractile Forces ◽  
Strain Responses

The intrinsic genetic program of a cell is not sufficient to explain all of the cell’s activities. External mechanical stimuli are increasingly recognized as determinants of cell behavior. In the epithelial folding event that constitutes the beginning of gastrulation in Drosophila, the genetic program of the future mesoderm leads to the establishment of a contractile actomyosin network that triggers apical constriction of cells and thereby tissue folding. However, some cells do not constrict but instead stretch, even though they share the same genetic program as their constricting neighbors. We show here that tissue-wide interactions force these cells to expand even when an otherwise sufficient amount of apical, active actomyosin is present. Models based on contractile forces and linear stress–strain responses do not reproduce experimental observations, but simulations in which cells behave as ductile materials with nonlinear mechanical properties do. Our models show that this behavior is a general emergent property of actomyosin networks in a supracellular context, in accordance with our experimental observations of actin reorganization within stretching cells.

scholarly journals Mechanical competition alters the cellular interpretation of an endogenous genetic programme

2020 ◽  
Author(s):  
Sourabh Bhide ◽  
Denisa Gombalova ◽  
Gregor Mönke ◽  
Johannes Stegmaier ◽  
Valentyna Zinchenko ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Emergent Property ◽  
Mechanical Stimuli ◽  
Cell Behaviour ◽  
Apical Constriction ◽  
Ductile Materials ◽  
A Cell ◽  
Contractile Forces ◽  
Strain Responses ◽  
Genetic Programme

AbstractThe intrinsic genetic programme of a cell is not sufficient to explain all of the cell’s activities. External mechanical stimuli are increasingly recognized as determinants of cell behaviour. In the epithelial folding event that constitutes the beginning of gastrulation in Drosophila, the genetic programme of the future mesoderm leads to the establishment of a contractile actomyosin network that triggers apical constriction of cells, and thereby, tissue folding. However, some cells do not constrict but instead stretch, even though they share the same genetic programme as their constricting neighbours. We show here that tissue-wide interactions force these cells to expand even when an otherwise sufficient amount of apical, active actomyosin is present. Models based on contractile forces and linear stress-strain responses do not reproduce experimental observations, but simulations in which cells behave as ductile materials with non-linear mechanical properties do. Our models show that this behaviour is a general emergent property of actomyosin networks [in a supracellular context, in accordance with our experimental observations of actin reorganisation within stretching cells.

scholarly journals Mechanical bistability enabled by ectodermal compression facilitates Drosophila mesoderm invagination

2021 ◽  
Author(s):  
Hanqing Guo ◽  
Michael Swan ◽  
Shicheng Huang ◽  
Bing He
Keyword(s):  
Myosin Ii ◽  
Cell Sheet ◽  
Apical Surface ◽  
Apical Constriction ◽  
Out Of Plane ◽  
A Cell ◽  
Plane Compression ◽  
Contractile Forces ◽  
Tissue Relaxation ◽  
Muscle Myosin

Apical constriction driven by non-muscle myosin II (″myosin″) provides a well-conserved mechanism to mediate epithelial folding. It remains unclear how contractile forces near the apical surface of a cell sheet drive out-of-plane bending of the sheet and whether myosin contractility is required throughout folding. By optogenetic-mediated acute inhibition of myosin, we find that during Drosophila mesoderm invagination, myosin contractility is critical to prevent tissue relaxation during the early, ″priming″ stage of folding but is dispensable for the actual folding step after the tissue passes through a stereotyped transitional configuration, suggesting that the mesoderm is mechanically bistable during gastrulation. Combining computer modeling and experimental measurements, we show that the observed mechanical bistability arises from an in-plane compression from the surrounding ectoderm, which promotes mesoderm invagination by facilitating a buckling transition. Our results indicate that Drosophila mesoderm invagination requires a joint action of local apical constriction and global in-plane compression to trigger epithelial buckling.

Tracings of Behavior of Myoblasts Cultured Under Couette Type of Shear Flow Between Parallel Disks

2021 ◽  
Author(s):  
Shigehiro Hashimoto ◽  
Hiroki Yonezawa
Keyword(s):  
Shear Stress ◽  
Shear Flow ◽  
Rotating Disk ◽  
Time Lapse ◽  
Mechanical Stimuli ◽  
Parallel Disks ◽  
Before And After ◽  
A Cell

Abstract A cell deforms and migrates on the scaffold under mechanical stimuli in vivo. In this study, a cell with division during shear stress stimulation has been observed in vitro. Before and after division, both migration and deformation of each cell were analyzed. To make a Couette-type shear flow, the medium was sandwiched between parallel disks (the lower stationary culture-disc and the upper rotating disk) with a constant gap. The wall shear stress (1.5 Pa < τ < 2 Pa) on the surface of the lower culture plate was controlled by the rotational speed of the upper disc. Myoblasts (C2C12: mouse myoblast cell line) were used in the test. After cultivation without flow for 24 hours for adhesion of the cells to the lower disk, constant τ was applied to the cells in the incubator for 7 days. The behavior of each cell during shear was tracked by time-lapse images observed by an inverted phase contrast microscope placed in the incubator. Experimental results show that each cell tends to divide after higher activities: deformation and migration. The tendency is remarkable at the shear stress of 1.5 Pa.

scholarly journals Localized mechanical stimulation of single cells with engineered spatio-temporal profile

Lab on a Chip ◽  
2018 ◽  
Vol 18 (19) ◽  
pp. 2955-2965 ◽  
Author(s):  
M. Monticelli ◽  
D. S. Jokhun ◽  
D. Petti ◽  
G. V. Shivashankar ◽  
R. Bertacco
Keyword(s):  
Cell Culture ◽  
Mechanical Stimulation ◽  
Single Cells ◽  
Mechanical Stimuli ◽  
Temporal Profile ◽  
A Cell ◽  
Spatio Temporal ◽  
Stimulation Of

We introduce a new platform for mechanobiology based on active substrates, made of Fe-coated polymeric micropillars, capable to apply mechanical stimuli with tunable spatio-temporal profile on a cell culture.

scholarly journals Phosphoregulation of the cytokinetic protein Fic1 contributes to fission yeast growth polarity establishment

2020 ◽  
Vol 133 (18) ◽  
pp. jcs244392
Author(s):  
K. Adam Bohnert ◽  
Anthony M. Rossi ◽  
Quan-Wen Jin ◽  
Jun-Song Chen ◽  
Kathleen L. Gould
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Behavior ◽  
Polarized Growth ◽  
Yeast Growth ◽  
Multiple Protein ◽  
A Cell ◽  
Growth Polarity ◽  
Polarity Regulation ◽  
Cellular Polarization

ABSTRACTCellular polarization underlies many facets of cell behavior, including cell growth. The rod-shaped fission yeast Schizosaccharomyces pombe is a well-established, genetically tractable system for studying growth polarity regulation. S. pombe cells elongate at their two cell tips in a cell cycle-controlled manner, transitioning from monopolar to bipolar growth in interphase when new ends established by the most recent cell division begin to extend. We previously identified cytokinesis as a critical regulator of new end growth and demonstrated that Fic1, a cytokinetic factor, is required for normal polarized growth at new ends. Here, we report that Fic1 is phosphorylated on two C-terminal residues, which are each targeted by multiple protein kinases. Endogenously expressed Fic1 phosphomutants cannot support proper bipolar growth, and the resultant defects facilitate the switch into an invasive pseudohyphal state. Thus, phosphoregulation of Fic1 links the completion of cytokinesis to the re-establishment of polarized growth in the next cell cycle. These findings broaden the scope of signaling events that contribute to regulating S. pombe growth polarity, underscoring that cytokinetic factors constitute relevant targets of kinases affecting new end growth.This article has an associated First Person interview with Anthony M. Rossi, joint first author of the paper.

A Study of Mechanosensing of an Osteoblast at Focal Adhesions Under Cyclic Strain Using Magnetic Micropillars

2019 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Kota Nagai
Keyword(s):  
Calcium Ion ◽  
Mechanical Vibration ◽  
Focal Adhesions ◽  
Cyclic Strain ◽  
Mechanical Stimuli ◽  
Osteoblast Cells ◽  
Intracellular Calcium Ion ◽  
A Cell ◽  
Sense And Respond ◽  
Biochemical Signals

Abstract It has been reported that cells sense and respond to mechanical stimuli. Mechanical vibration promotes the cell proliferation and the cell differentiation of osteoblast cells at 12.5 Hz and 50 Hz, respectively. It indicates that osteoblast cells have a mechansensing system for mechanical vibration. There may be some mechanosensors and we focus on cellular focal adhesions through which mechanical and biochemical signals may be transmitted from extracellular matrices into a cell. However, it is very difficult to directly apply mechanical stimuli to focal adhesions. We developed a magnetic micropillar substrate on which micron-sized pillars are deflected according to applied magnetic field strength and focal adhesions adhering to the top surface of the pillars are given mechanical stimuli. In this paper, we focus on intracellular calcium ion as a second messenger of cellular mechanosensing and investigate the mechanosensing mechanism of an osteoblast cell at focal adhesions under cyclic strain using a magnetic micropillar substrate. The experimental results indicate that the magnetic micropillars have enough performance to response to an electric current applied to a coil in an electromagnet and to apply the cyclic strain of less than 3% to a cell. In the cyclic strain of less than 3%, the calcium response of a cell was not observed.

scholarly journals Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

2020 ◽  
Vol 21 (20) ◽  
pp. 7595
Author(s):  
Anita K. Luu ◽  
Alicia M. Viloria-Petit
Keyword(s):  
Tumour Progression ◽  
Cell Signalling ◽  
Bone Tumour ◽  
Mechanical Stimuli ◽  
Current State ◽  
Organ Systems ◽  
A Cell ◽  
Canine Models ◽  
Improved Design ◽  
And Function

Mechanotransduction is the process in which cells can convert extracellular mechanical stimuli into biochemical changes within a cell. While this a normal process for physiological development and function in many organ systems, tumour cells can exploit this process to promote tumour progression. Here we summarise the current state of knowledge of mechanotransduction in osteosarcoma (OSA), the most common primary bone tumour, referencing both human and canine models and other similar mesenchymal malignancies (e.g., Ewing sarcoma). Specifically, we discuss the mechanical properties of OSA cells, the pathways that these cells utilise to respond to external mechanical cues, and mechanotransduction-targeting strategies tested in OSA so far. We point out gaps in the literature and propose avenues to address them. Understanding how the physical microenvironment influences cell signalling and behaviour will lead to the improved design of strategies to target the mechanical vulnerabilities of OSA cells.

scholarly journals Integration of contractile forces during tissue invagination

2010 ◽  
Vol 188 (5) ◽  
pp. 735-749 ◽  
Author(s):  
Adam C. Martin ◽  
Michael Gelbart ◽  
Rodrigo Fernandez-Gonzalez ◽  
Matthias Kaschube ◽  
Eric F. Wieschaus
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Adherens Junction ◽  
Tissue Level ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Contractile Forces ◽  
Actomyosin Cytoskeleton ◽  
Cellular Forces ◽  
Anterior Posterior

Contractile forces generated by the actomyosin cytoskeleton within individual cells collectively generate tissue-level force during epithelial morphogenesis. During Drosophila mesoderm invagination, pulsed actomyosin meshwork contractions and a ratchet-like stabilization of cell shape drive apical constriction. Here, we investigate how contractile forces are integrated across the tissue. Reducing adherens junction (AJ) levels or ablating actomyosin meshworks causes tissue-wide epithelial tears, which release tension that is predominantly oriented along the anterior–posterior (a-p) embryonic axis. Epithelial tears allow cells normally elongated along the a-p axis to constrict isotropically, which suggests that apical constriction generates anisotropic epithelial tension that feeds back to control cell shape. Epithelial tension requires the transcription factor Twist, which stabilizes apical myosin II, promoting the formation of a supracellular actomyosin meshwork in which radial actomyosin fibers are joined end-to-end at spot AJs. Thus, pulsed actomyosin contractions require a supracellular, tensile meshwork to transmit cellular forces to the tissue level during morphogenesis.

scholarly journals Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis

2014 ◽  
Vol 206 (3) ◽  
pp. 435-450 ◽  
Author(s):  
Claudia G. Vasquez ◽  
Mike Tworoger ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Epithelial Morphogenesis ◽  
Nonmuscle Myosin ◽  
Apical Constriction ◽  
Tissue Integrity ◽  
Cell Shape Change ◽  
Nonmuscle Myosin Ii ◽  
A Cell ◽  
Coupling Dynamic

Apical constriction is a cell shape change that promotes epithelial bending. Activation of nonmuscle myosin II (Myo-II) by kinases such as Rho-associated kinase (Rok) is important to generate contractile force during apical constriction. Cycles of Myo-II assembly and disassembly, or pulses, are associated with apical constriction during Drosophila melanogaster gastrulation. It is not understood whether Myo-II phosphoregulation organizes contractile pulses or whether pulses are important for tissue morphogenesis. Here, we show that Myo-II pulses are associated with pulses of apical Rok. Mutants that mimic Myo-II light chain phosphorylation or depletion of myosin phosphatase inhibit Myo-II contractile pulses, disrupting both actomyosin coalescence into apical foci and cycles of Myo-II assembly/disassembly. Thus, coupling dynamic Myo-II phosphorylation to upstream signals organizes contractile Myo-II pulses in both space and time. Mutants that mimic Myo-II phosphorylation undergo continuous, rather than incremental, apical constriction. These mutants fail to maintain intercellular actomyosin network connections during tissue invagination, suggesting that Myo-II pulses are required for tissue integrity during morphogenesis.

Sign in / Sign up

Export Citation Format

Share Document