scholarly journals The nucleus measures shape changes for cellular proprioception to control dynamic cell behavior

Science ◽  
2020 ◽  
Vol 370 (6514) ◽  
pp. eaba2644 ◽  
Author(s):  
Valeria Venturini ◽  
Fabio Pezzano ◽  
Frederic Català Castro ◽  
Hanna-Maria Häkkinen ◽  
Senda Jiménez-Delgado ◽  
...  

The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within tissues remains largely unknown. Here, using a zebrafish model, we show that the nucleus, the biggest cellular organelle, functions as an elastic deformation gauge that enables cells to measure cell shape deformations. Inner nuclear membrane unfolding upon nucleus stretching provides physical information on cellular shape changes and adaptively activates a calcium-dependent mechanotransduction pathway, controlling actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behavior to their microenvironment.

2019 ◽  
Author(s):  
Valeria Venturini ◽  
Fabio Pezzano ◽  
Frederic Català Castro ◽  
Hanna-Maria Häkkinen ◽  
Senda Jiménez-Delgado ◽  
...  

AbstractThe physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within their local environment remains largely unknown. Here we show that the nucleus, the biggest cellular organelle, functions as a non-dissipative cellular shape deformation gauge that enables cells to continuously measure shape variations on the time scale of seconds. Inner nuclear membrane unfolding together with the relative spatial intracellular positioning of the nucleus provides physical information on the amplitude and type of cellular shape deformation. This adaptively activates a calcium-dependent mechano-transduction pathway, controlling the level of actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behaviour to their microenvironment.One Sentence SummaryThe nucleus functions as an active deformation sensor that enables cells to adapt their behavior to the tissue microenvironment.


Micromachines ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 308 ◽  
Author(s):  
Phalguni Tewari Kumar ◽  
Deborah Decrop ◽  
Saba Safdar ◽  
Ioannis Passaris ◽  
Tadej Kokalj ◽  
...  

When screening microbial populations or consortia for interesting cells, their selective retrieval for further study can be of great interest. To this end, traditional fluorescence activated cell sorting (FACS) and optical tweezers (OT) enabled methods have typically been used. However, the former, although allowing cell sorting, fails to track dynamic cell behavior, while the latter has been limited to complex channel-based microfluidic platforms. In this study, digital microfluidics (DMF) was integrated with OT for selective trapping, relocation, and further proliferation of single bacterial cells, while offering continuous imaging of cells to evaluate dynamic cell behavior. To enable this, magnetic beads coated with Salmonella Typhimurium-targeting antibodies were seeded in the microwell array of the DMF platform, and used to capture single cells of a fluorescent S. Typhimurium population. Next, OT were used to select a bead with a bacterium of interest, based on its fluorescent expression, and to relocate this bead to a different microwell on the same or different array. Using an agar patch affixed on top, the relocated bacterium was subsequently allowed to proliferate. Our OT-integrated DMF platform thus successfully enabled selective trapping, retrieval, relocation, and proliferation of bacteria of interest at single-cell level, thereby enabling their downstream analysis.


Data ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 71 ◽  
Author(s):  
Diana Victoria Ramírez López ◽  
María Isabel Melo Escobar ◽  
Carlos A. Peña-Reyes ◽  
Álvaro J. Rojas Arciniegas ◽  
Paola Andrea Neuta Arciniegas

Regenerative medicine involves methods to control and modify normal tissue repair processes. Polymer and cell constructs are under research to create tissue that replaces the affected area in cardiac tissue after myocardial infarction (MI). The aim of the present study is to evaluate the behavior of differentiated and undifferentiated mesenchymal stem cells (MSCs) in vitro and in silico and to compare the results that both offer when it comes to the design process of biodevices for the treatment of infarcted myocardium in biomodels. To assess in vitro behavior, MSCs are isolated from rat bone marrow and seeded undifferentiated and differentiated in multiple scaffolds of a gelled biomaterial. Subsequently, cell behavior is evaluated by trypan blue and fluorescence microscopy, which showed that the cells presented high viability and low cell migration in the biomaterial. An agent-based model intended to reproduce as closely as possible the behavior of individual MSCs by simulating cellular-level processes was developed, where the in vitro results are used to identify parameters in the agent-based model that is developed, and which simulates cellular-level processes: Apoptosis, differentiation, proliferation, and migration. Thanks to the results obtained, suggestions for good results in the design and fabrication of the proposed scaffolds and how an agent-based model can be helpful for testing hypothesis are presented in the discussion. It is concluded that assessment of cell behavior through the observation of viability, proliferation, migration, inflammation reduction, and spatial composition in vitro and in silico, represents an appropriate strategy for scaffold engineering.


Author(s):  
Wenwei Xu ◽  
Roman Mezencev ◽  
Byungkyu Kim ◽  
Lijuan Wang ◽  
John McDonald ◽  
...  

Cancer cells undergo a variety of biochemical and biophysical transformations when compared to identical cells displaying a healthy phenotypic state, cancer cells show a drastic reduction of stiffness upon malignancy[1, 2] and change of stiffness of single cells can indicate the presence of disease [3–6]. Besides, metastatic cancer has a higher deformability than their benign counterparts[7, 8]. Using atomic force microscopy, we demonstrated that cancerous ovarian cells (OVCAR3, OVCAR4, HEY and HEYA8) are substantially softer than the healthy immortalized ovarian surface epithelium (IOSE) cells. In addition, within the different types of cancerous ovarian cells, increased invasiveness and migration are directly correlated with increased cell deformability. These results indicate that stiffness of individual cells can distinguish not only ovarian cancer cells from healthy cells types, but also invasive cancer types from less invasive types. Stiffness may provide an alternative and convenient biomarker to grade the metastasis potential of cancer cells.


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