Art is Life? Cell Tensegrity - Artefact of Fact?

[jimmydasaint]

Professor Ingber of Harvard Medical School seems to refer to art and architecture in his cellular tensegrity model.

 

The cellular tensegrity model proposes that the whole cell is a prestressed tensegrity structure, although geodesic structures are also found in the cell at smaller size scales (e.g. clathrin-coated vesicles, viral capsids). In the model, tensional forces are borne by cytoskeletal microfilaments and intermediate filaments, and these forces are balanced by interconnected structural elements that resist compression, most notably internal microtubule struts and ECM adhesions. However, individual filaments can have dual functions and hence bear either tension or compression in different structural contexts or at different size scales

 

http://web1.tch.harvard.edu/research/ingber/Tensegrity.html

 

Ultimately, it may suggest that nuclear and cellular gene expression is changed due to the architectural configuration and the environment of the cell. I just want to suggest a discussion on whether his findings are artefact or fact (excuse me for the pun in advance), or has he gone too far in stressing the architectural beauty of the cell and ignored the biological complexities of the cellular milieu?

 

on flexible-puckering surface - rounded nucleus

 

on rigid surface - flattened nucleus

 

Ingber's view of the cell as a tensegrity structure may help explain why cells in tissue culture spread out and flatten when grown on rigid glass of plastic petri dishes, but when on a flexible surface the cells contract and become spherical.

 

Ingber modeled a cell as a tensegrity structure made of six wood dowels and elastic string. The wooden dowels occurred in three pairs, each perpendicular to the other two and bore the compressive stress. Tension bearing elastic string connected to the ends of the dowels, pulling them into a stable, 3-D form. A smaller, spherical tensegrity model, inside the larger one, represented thecell's nucleus. Stretched elastic strings between the nucleus and dowels mimicked cytoskeletal connections.

 

Applying downward force on the tensegrity cell model shapes it into a flattened pile of sticks and string. When the force is removed, the energy stored in the tensed filaments causes the cell model to spring back to its original, roughly spherical shape. The pictures above from Ingber's article's suggest how cells may behave when placed on a rigid or flexible surfaces.

 

When attached to a taut, stretched piece of cloth the model flattens and spread out. The model's attachment to the flat cloth is analogous to the adhesion receptors (integrins) which physically connect a cell to an anchoring basement membrane substratum.

 

http://www.bio.miami.edu/~cmallery/255/255chem/tensegritymodel.htm#2

[Mokele]

He's made a critical error in scale - at the scale of most cells, inertial and gravitational forces are completely swamped out by fluid forces. If you shrunk to the size of a large eukaryote cell, you'd feel like you were swimming through syrup. If you shrunk to the size of a bacteria, it'd feel like swimming in tar. Given that cells are almost the same density as the surrounding medium, there's not really much force flattening them.

 

I also wonder how much of a role his model of the cytoskeleton plays compared to osmotic pressurization caused concentration gradient.

[jimmydasaint]

He actually takes into account pre-stress caused by osmosis as a passive mechanism contributing to the cellular architecture. However, the research owes much to the work of Buckminster Fuller. If Ingber's work has merit then it is ground-breaking in its scope. We are talking about contributions towards cellular differentiation, developmental biology and also to the genesis of tumours. I have also looked up one of his publications which seems to implicate 'extracellular matrix elasticity' and this is amazing! It suggests that gene expression is also controlled by the mechanical actions of the extracellular environment.

 

A mechanosensitive transcriptional mechanism that controls angiogenesis.

 

Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LE, Ingber DE.

Vascular Biology Program, Department of Pathology & Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Angiogenesis is controlled by physical interactions between cells and extracellular matrix as well as soluble angiogenic factors, such as VEGF. However, the mechanism by which mechanical signals integrate with other microenvironmental cues to regulate neovascularization remains unknown. Here we show that the Rho inhibitor, p190RhoGAP (also known as GRLF1), controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between two antagonistic transcription factors, TFII-I (also known as GTF2I) and GATA2, that govern gene expression of the VEGF receptor VEGFR2 (also known as KDR). Moreover, this new angiogenesis signalling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF. This is, to our knowledge, the first known functional cross-antagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.

 

http://www.ncbi.nlm.nih.gov/pubmed/19242469?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

[smlevin]

I am an enthusiast of Ingber's concept of cells as tensegrities, but on this point, I strongly disagree. Tensegrities do not squish, but symmetrically contract. To quote Fuller,“ … if concentrated load is applied from without, the whole system contracts symmetrically, i.e., all vertices move toward their common center at the same rate.” [synergetics 724.32-34]. This phenomenon is a sine qua non of tensegrity structures and is illustrated by the works of Rossiter, Burkhardt, Wolfram and so many others who know, understand and love tensegrity. The error occurs when the model used to understand tensegrity uses weak elastics as the tension elements. In true tensegrities, the tension elements get stiffer as the structure is loaded, but not so in the rubber band models. If you use nylon-fishing line, as does Hamilton, the response to loading more closely represents true tensegrities.

I have put this, with appropriate illustrations in my blog at, http://tinyurl.com/b10-shear.

[lucaspa]

He's made a critical error in scale - at the scale of most cells, inertial and gravitational forces are completely swamped out by fluid forces. If you shrunk to the size of a large eukaryote cell, you'd feel like you were swimming through syrup. If you shrunk to the size of a bacteria, it'd feel like swimming in tar. Given that cells are almost the same density as the surrounding medium, there's not really much force flattening them.

 

He's not talking about gravity. He's talking forces on the cell. Those forces are often exerted thru the proteins that attach the cell to the extracellular matrix: "The model's attachment to the flat cloth is analogous to the adhesion receptors (integrins) which physically connect a cell to an anchoring basement membrane substratum. " Endothelial and smooth muscle cells are subjected to flow forces as they are attached to the matrix of an artery.

 

I also wonder how much of a role his model of the cytoskeleton plays compared to osmotic pressurization caused concentration gradient.

 

Quite a bit. It's also correct that "nuclear and cellular gene expression is changed due to the architectural configuration and the environment of the cell. " This has been known for 20 years in the field of cartilage biology. Grow chondrocytes on plastic and they flatten out, express collagen type I, and small proteoglycans. Change the shape by growing chondrocytes in agar or coating the plastic with HEPES and the cells are spherical, synthesize type II collagen, large aggrecan, and generally make a cartilage matrix. You can take them thru several cyles of regular plastic and HEPES plastic and have them flatten and behave like fibroblasts and then behave like chondrocytes.

 

I've attended a couple of talks about cell shape and tensigrity and the data seems valid.

[jimmydasaint]

Note to self - don't post any thread during exam season. Having just marked a pile of exam papers, I have a short time to respond before marking the next tranche -groan!

 

I have just looked over your blog doc levin. You have written:

 

The next question has to be, “Does the cell deform as a tensegrity or as a linear material?” No doubt, when individual cells are tested on a slide, the appear to have the linear deformities as in Xuan’s illustrations, but cells in biologic tissues are never alone, they interact in concert. The mechanical response may be quite different when cells are crowded together interacting with their buddies, much like a single isolated bubble reacts differently than a bubble acting as part of a foam (Wikipedia: Foam). I don’t know if any one has actually studied this. I am open to see further research.

 

I agree that cells may not behave in vivo as they do in vitro. However, having said that, I have also read about rearrangement of the cytoskeleton depending on the immediate solid environment. lucaspa summarises it quite concisely:

This has been known for 20 years in the field of cartilage biology. Grow chondrocytes on plastic and they flatten out, express collagen type I, and small proteoglycans. Change the shape by growing chondrocytes in agar or coating the plastic with HEPES and the cells are spherical, synthesize type II collagen, large aggrecan, and generally make a cartilage matrix.

 

However, doc, your comments about the cell rearranging as a tensegrity structure are intriguing if they can be verified. I saw Guimberteau's movie but cannot clearly see the structures rearrange as clearly as you can. I don't doubt what you say but where is the prima facie evidence for it?