Ingber, Donald A
Read here about Professor Donald Ingber, one of the first mainstream biological researchers to posit tensegrity as the best explanation for mechanobiological structure. Due to his work, the cytoskeleton is now widely believed to be a tensegrity structure, and tensegrity mechanics at the cellular level is now close to replacing all previous mechanical models of the cell.
Ingber has demonstrated a direct tensegrity-type link between the surface of the cell and the cell nucleus [3].
Short Biography of Ingber
Donald A. Ingber is Senior Associate in Pathology and Surgery of the Vascular Biology Program, Judah Folkman Professor in Vascular Biology, Harvard Medical School. He simultaneously received his MD and PhD from Yale University. He is credited on over 20 patents which cover technologies ranging from new cancer drugs and drug-screening assays to medical devices, micromanufacturing techniques, and computer software.
Donald Ingber is interested in how cell structure and mechanics impact cellular biochemistry and tissue development. His research approach has combined techniques from various fields, including molecular cell biology, engineering, chemistry, physics, and computer science.
Tensegrity Concepts in Ingber's Work
Inspired by Snelson
Ingber wrote in [4]: "Strangely, my story starts in an undergraduate art class, which I elected to take even though I was a science major. One day my professor brought in a ‘tensegrity’ sculpture into class made of sticks and elastic strings that looked much like this toy I am holding before you right now. This structure is composed of sticks connected by elastic strings. Without the sticks, the network of strings would lose its shape and become limp, like a spider web cut from its attachments. But because the sticks resist the inward pull of the strings, the whole structure is placed in a state of isometric tension that stabilizes it in this round form. The tensegrity building system was first described by Buckminster Fuller, the inventor of the geodesic dome, and the sculptor Kenneth Snelson. It gains its shape stability by balancing tension and compression between struts and strings, just like bones and muscles do in our body. For example, the stiffness of my extended arm depends on the level of isometric tension or ‘tone’ in muscles, just like in this model.
"As my art professor spoke, he pushed this round sculpture flat, and when he let go, it leapt up in the air. This was interesting, because I had seen the same behavior just days before when I first learned how to culture cells across the campus in a medical school laboratory. Cells flatten when they adhere to a culture dish, but when you detach them, they round up and jump off the dish just like this toy. This was in the mid 1970s when people still thought of cells like water balloons filled with molasses. But scientists had recently discovered that all cells have an internal skeleton made of molecular ‘acto-myosin’ filaments that generate mechanical tension, as in muscle. So I just assumed that cells must be tensegrity structures.
"Later, when I went back to the medical school lab, and saw cancer cells changing shape under the microscope in response to a drug we were testing, I spurted out something like, 'Oh, the tensegrity must have changed'. The postdoc I was working with said, 'What did you say?', and I explained about my art class and Buckminster Fuller, and the sculptor Snelson, and sticks and strings; and he said, 'Well, never say that again'. And, as they say, that was the beginning of the rest of my life."
Mechanical forces regulate cellular activity
Nancy Fleiser wrote, "Ingber argues that mechanical forces - pushes, pulls, tensions, compressions - are important regulators of cell development and behavior. Tensegrity provides the structure - the architecture if you will - that determines how these physical forces are distributed inside a cell or tissue, and how and where they exert their influence... In trying to reestablish a physical view of biology, Ingber has shown that cells, far from being formless blobs, use tension to stabilize their structure. And he has demonstrated, through two decades of experiments, that tensegrity not only gives cells their shape, but helps regulate their biochemistry."
Ingber [2] uses tensegrity as Fuller describes it in [section 784]. He posits the tension and compression elements of the cytoskeleton as follows, though he does not stipulate the precise mechanics of the implementation:
- Compression: tubulin, a stiff component, and
- Tension: actin, a tension component
The cytoskeleton is a tensegrity scaffold
Ingber focuses on the internal scaffold or cytoskeleton of the cell. This is a lattice that can be divided into tension and compression members, not unlike the division into tubes and wires that you see in a Snelson sculpture. Fleiser wrote, "The 'wires' are a crisscrossing network of fine cables, known as microfilaments, that stretch from the cell membrane to the nucleus, exerting an inward pull. Opposing the pull are microtubules, the thicker compression-bearing "struts" of the cytoskeleton, and specialized receptor molecules on the cell's outer membrane that anchor the cell to the extracellular matrix, the fibrous substance that holds groups of cells together. This balance of forces is the hallmark of tensegrity." The cell's components position and role in the tensegrity is integrated as well into their bioinformatic functionality.
Tension-bearing members are geodesic
"The tension-bearing members in these structures – whether Fuller's domes or Snelson's sculptures – map out the shortest paths between adjacent members (and are therefore, by definition, arranged geodesically) Tensional forces naturally transmit themselves over the shortest distance between two points, so the members of a tensegrity structure are precisely positioned to best withstand stress. For this reason, tensegrity structures offer a maximum amount of strength."
Multimedia on the web featuring Ingber
This clip is from Dr. Donald Ingber's talk on "The Relevance of Tensegrity Architecture for Biology and Medicine" at the Synergetics Collaborative Fall 2005 Symposium on "Synergetics in the Arts" at the Noguchi Museum. Donald talks about how cell structure is inherently built on the principles of tensegrity.
Donald Ingber on Tensegrity Architecture and Cell Structure
This clip is from Dr. Donald Ingber's talk on "The Relevance of Tensegrity Architecture for Biology and Medicine" at the Synergetics Collaborative Fall 2005 Symposium on "Synergetics in the Arts" at the Noguchi Museum. Donald talks about how cell structure is inherently built on the principles of tensegrity.
Link: https://www.youtube.com/watch?v=AT5fsO95-qg
=Partial List of Works by Ingber
R. W. Gray posted a partial list of references to Donald Ingber's, et. al., work on modeling cell structure and function with tensegrity structures.
- Chen CS, Ingber DE. Tensegrity and mechanoregulation: from skeleton to cytoskeleton. Osteoarthritis and Articular Cartilage (January 1999-in press
- Chicurel M, Chen CS, Ingber DE. Cellular control lies in the balance of forces. Curr. Opin. Cell Biol. 1998; 10:232-239.
- Ingber, D.E., The Architecture of Life. Scientific American Jan 1998; 278:48-57.
- Ingber D.E., Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 1997; 59:575-599.
- Ingber D.E., Integrins, tensegrity, and mechanotransduction. Grav. and Space Bio. Bultn. 1997; 10:49-55.
- Maniotis A, Chen C, Ingber DE. Demonstration of mechanical connections between integrins, cytoskeletal filaments and nucleoplasm that stabilize nuclear structure. Proc. Natl. Acad. Sci. U.S.A. 1997; 94:849-854.
- Maniotis A, Bojanowski K, Ingber DE. Mechanical continuity and reversible chromosome disassembly within intact genomes microsurgically removed from living cells. J. Cellul. Biochem. 1997; 65:114-130.
- Dimitrije S., Fredberg J., Wang N., Butler J., Ingber D.E., A Microstructural Approach to Cytoskeletal Mechanics Based on Tensegrity, J. Theor. Biol., Vol. 181, pp. 125-136, 1996
- Stamenovic D, Fredberg J, Wang N, Butler J, Ingber D. A microstructural approach to cytoskeletal mechanics based on tensegrity. J. Theor. Biol. 1996; 181:125-136.
- Wang N., Ingber D.E., Control of Cytoskeletal Mechanics By Extracellular matrix, Cell Shape, and Mechanical Tension, Biophys. J., Vol. 66, pp. 2181-2189, 1994
- Ingber D.E., Dike L., Hansen L., Karp S., Liley H., Maniotis A., McNamee H., Mooney D., Plopper G., Sims J., Wang N., Cellular Tensegrity: Exploring How Mechanical Changes in the Cytoskeleton Regulate Cell Growth, Migration, and Tissue Pattern During Morphogenesis, Int. Rev. Cytol, Vol. 150, pp. 173-224, 1994
- Ingber D.E., The Riddle of Morphogenesis: A Question of Solution Chemistry or Molecular Cell Engineering?, Cell, Vol. 75, pp. 1249-1252, 1993
- Wang, N., Butler J.P., Ingber D.E., Mechanotransduction Across the Cell Surface and Through the Cytoskeleton, Scinece, Vol. 260, pp. 1124-1127, 1993
- Ingber D.E., Cellular Tensegrity: Defining New Rules of Biological Design That Govern The Cytoskeleton, J. Cell Sci., Vol. 104, pp. 613-627, 1993
Link to Robert W. Gray's original list: [[1]]
Inspired by the Needle Tower
The Needle Tower is documented as being the inspiration for Ingber's work. He tells the story in an episode of "Arts & Ideas" in 2006. See https://www.wnyc.org/story/108562-the-science-of-sculpture/
Critiques of Ingber's Approach
Some critiques of Ingber's approach.
Snelson Claims Ingber's approach is more Geodesic Geometry than Tensegrity
Snelson wrote, "the Harvard microbiologist Donald Ingber invokes tensegrity as a buzzword to bolster a contested theory of cell structure. To him, a geodesic dome is synonymous with tensegrity." [1]
Selected Readings by Ingber
A selection of Ingber's work can be read here via Scribd. They are divided roughly into general and specialized articles.
General
Ingber's work presented to a general audience, be it an article for laymen, a summary of the state of the art, or a keynote address. These readings give a good overview of issues.
Architecture of Life
Architecture of Life Scientific American by Ingber http://www.scribd.com/doc/35190367/Architecture-of-Life-Scientific-American-by-Ingber
Donald E. Ingber's precedent-setting article in the Janary 1998 issue of Scientific American. Ingber's research has since advanced considerably, see his website at http://web1.tch.harvard.edu/research/ingber/Tensegrity.html. An article on Ingber in the Encyclopedia of Tensegrity is hosted on the wiki here, http://tensegrity.wikispaces.com/Ingber,+Donald+A
Dartmouth Medical School Keynote
Keynote Dartmouth Medical School June 2009 by Ingber
http://www.scribd.com/doc/35312249/Keynote-Dartmouth-Medical-School-June-2009-by-Ingber
Keynote Speech Dartmouth Medical School Class Day June 13, 2009 by Donald E. Ingber, MD, PhD
From Cellular Mechanotransduction to Biologically Inspired Engineering
Ingber lecture: From Cellular Mechanotransduction to Biologically Inspired Engineering
Ingber's 2009 Pritzker Award Lecture provides a great overview of the state of cell cytoskeleton comprehension in terms of tensegrity. Ingber divides his talk into eight sections: 1. The living cell as a mechanical structure, 2. A strange idea: tensegrity in cells, 3. Engineering approaches provide new insights into cell structure, 4. Integrins as mechanoreceptors, 5. Structural hierarchies for force transmission in living systems, 6. Solid-state biochemistry and cellular mechanotransduction, 7. Mechanical control of cell function and tissue development and 8. Bioinspired technology fallout. The talk includes a good overview of tensegrity, and details on cell shape stability mechanisms, such as force balances between compressive microtubule struts and tensile actomyosin filaments. He also describes the activity of integrin receptors in the scope of the model. Ingber finds the global nature of tensegrity a good explanation for the behavior of transmembrane surface receptor molecules (e.g., growth factor receptors, integrins, cadherins) and how they induce shape transitions at their cytoplasmic faces, mediating transmembrane signaling. For more details, see http://www.childrenshospital.org/research/ingber/ or http://tensegrity.wikispaces.com/Portal+To+Cellular+Biology
Cells and Micro Gravity
How Cells (Might) Sense Micro Gravity by Ingber http://www.scribd.com/doc/29350783/How-Cells-Might-Sense-Micro-Gravity-by-Ingber
This article is a summary of a lecture presented at an ESA/NASA Workshop on Cell and Molecular Biology Research in Space that convened in Leuven, Belgium, in June 1998. Recent studies are reviewed which suggest that cells may sense mechanical stresses, including those due to gravity, through changes in the balance of forces that are transmitted across transmembrane adhesion receptors that link the cytoskeleton to the extracellular matrix and to other cells (e.g., integrins, cadherins, selectins). The mechanism by which these mechanical signals are transduced and converted into a biochemical response appears to be based, in part, on the finding that living cells use a tension-dependent form of architecture, known as tensegrity, to organize and stabilize their cytoskeleton. Because of tensegrity, the cellular response to stress differs depending on the level of pre-stress (pre-existing tension) in the cytoskeleton and it involves all three cytoskeletal filament systems as well as nuclear scaffolds. Recent studies confirm that alterations in the cellular force balance can influence intracellular biochemistry within focal adhesion complexes that form at the site of integrin binding as well as gene expression in the nucleus. These results suggest that gravity sensation may not result from direct activation of any single gravioreceptor molecule. Instead, gravitational forces may be experienced by individual cells in the living organism as a result of stress-dependent changes in cell, tissue, or organ structure that, in turn, alter extracellular matrix mechanics, cell shape, cytoskeletal organization, or internal pre-stress in the cell-tissue matrix.
Cell Structure and Hierarchical Systems
Tensegrity I. Cell Structure and Hierarchical Systems by Ingber http://www.scribd.com/doc/35313348/Tensegrity-I-Cell-Structure-and-Hierarchical-Systems-by-Ingber
Tensegrity I. Cell structure and hierarchical systems biology, by Donald E. Ingber. Journal of Cell Science 116, 1157-1173 © 2003 The Company of Biologists Ltd doi:10.1242/jcs.00359
Opposing Views on Tensegrity in Cell Mechanics
Opposing Views on Tensegrity as a Structural Framework for Understanding Cell Mechanics by Ingber http://www.scribd.com/doc/35312634/Opposing-Views-on-Tensegrity-as-a-Structural-Framework-for-Understanding-Cell-Mechanics-by-Ingber
Opposing Views on Tensegrity as a Structural Framework for Understanding Cell Mechanics by Donald E. Ingber, Steven R. Heidemann, Phillip Lamoureux and Robert E. Buxbaum
Specialized Readings
Readings that take a deep dive into a particular, specialized topic.
New Rules That Govern the Cytoskeleton
Cellular Tensegrity Defining New Rules of Biological Design That Govern the Cytoskeleton by Ingber
Journal of Cell Science 104, 613-627 (1993). Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton by Donald E. Ingber
Diseases of Mechanotransduction
Mechanobiology and Diseases of Mechanotransduction by Ingber
http://www.scribd.com/doc/35312433/Mechanobiology-and-Diseases-of-Mechanotransduction-by-Ingber
Integrins and Mechanotransduction
Integrins Tensegrity and Mechanotransduction by Ingber
http://www.scribd.com/doc/35312202/Integrins-Tensegrity-and-Mechanotransduction-by-Ingber
Abstract: Physical forces, such as those due to gravity, play an important role in tissue development and remodeling, Yet, little is known about how individual cells sense mechanical signals or how they transduce them into a chemical response, Rather than listing the numerous signal pathways that have been found to be...
Pre-Stressed Tensegrity DNA Structures
2D and 3D Pre-Stressed Tensegrity DNA Structures by Liedl, Ingber, Shih
A short powerpoint presentation by Tim Liedl, Donald E. Ingber, William M. Shih reviewing hte comparison between human-created tensegrity architectural structures on a building and sculptural scale, and natural and human-made tensegrities on the nano scale. The slide headings are (1) Excursion to Architecture: Continuous compression (2) Tensegrity - Tensional Integrity (3) Pre-stressed tensegrity design in architecture (4) Pre-stressed tensegrity in natureDNA cube (5) DNA Nanotechnology and (6) Future Directions. For more information about Ingber, see his website, http://web1.tch.harvard.edu/research/ingber/Tensegrity.html, or visit http://tensegrity.wikispaces.com/Ingber,+Donald+A
Cellular Mechanotransduction
Tensegrity-Based Mechanosensing From Macro to Micro, Summary of a Lecture on Cellular Mechanotransduction By Ingber
Tensegrity-based mechanosensing from macro to micro by Donald E. Ingber. Abstract This article is a summary of a lecture on cellular mechanotransduction.
Cellular Information Processing Networks
How Structural Networks Influence Cellular Information Processing Networks by Ingber
How structural networks influence cellular information processing networks by Donald E. Ingber
Mechanical Control of Cell Fate Switching and Morphogenesis
Tensegrity-Based Mechanical Control of Mammalian Cell Fate Switching and Morphogenesis by Ingber
A powerpoint presentation by Ingber, the world's leading proponent of a tensegrity-based view of cellular structure. The slide deck includes: How are living cells and tissues constructed? A linear view of tissue development(tumor angiogenesis). Local control during angiogenesis, with branching patterns. Extracellular matrix: cells exert tension on their matrix adhesions. Micromechanical control of morphogenesis. Underlying hypothesis: Ecm remodeling changes local mechanics, Increasing ecm flexibility promotes cell stretching, Tension on adhesion receptors & distortion of the cytoskeleton alters cellular biochemistry. Laboratory evidence shows, stretching cells makes them grow and rounded cells die. Cell distortion redirects molecular self-assembly in the cytoskeleton & extracellular matrix guided by localized tension application in cell corners. Local rules & physical determinants govern pattern formation (“symmetry breaking” in mammalian cells). Patterning predicted by whole cell behaviors. Cell fate switching depends on physicality of microenvironment: spatial heterogeneity of cell fates drives morphogenesis. How are cells constructed so that they can sense force? Old view: cells are like water balloons. New view: cells are built like tensegrities, or tensile structured tents. Evidence for this: Resting tension (prestress) in living stress fibers revealed using laser nano-surgery (“tensed cables”), microtubules are semi- flexible compression struts, tensegrity predicts adhesion receptors act as mechanoreceptors, magnetic twisting & pulling cytometry. Research has confirmed many tensegrity model predictions such as (1) Linear relation between stiffness and applied stress (2) Cell mechanics depends on prestress (3) Linear relation between stiffness and prestress (4) Hysteresivity independent of prestress (5) Quantitative prediction of cellular elasticity (6) Prediction of dynamic mechanical behavior (7) Mechanical contribution of intermediate filaments to cell mechanics (8) Microtubules bear compression (9) A local stress can produce distant responses (10) Cortical membrane acts as a prestressed tensegrity. Tensegrity focuses force on molecules in the extracellular matrix and cytoskeleton. Tensegrity provides a mechanism to integrate both local and distant structural responses when forces are transmitted through the cytoskeleton. Signal integration through cell distortion: cells act locally, but “think” globally. Extracellular matrix & cytoskeleton not just structural supports they also are key developmental regulators because they mediate mechanical signaling: a Network model explains their decision making better than a linear model.
Links and References
Ingber's website: http://web1.tch.harvard.edu/research/ingber/homepage.htm%7CIngber Lab Home Page
Email: Ingber can be reached by email at donald.ingber on the Children's Hospital Boston domain, childrens.harvard.edu
Ingber Interview on Arts & Ideas, The Science of Sculpture, Studio 360, produced by Lu Olkowski, originally aired: May 12, 2006.[2]]
[1] Letter from Kenneth Snelson to Maria Gough June 17, 2003, retrieved 18 Feb. 2010 from Burkhardt's website, [[3]]
[2] Ingber, D. E. (1993). Cellular tensegrity: Defining new rules of biological design that govern the cytoskeleton. Journal of Cell Science, 104 ( Pt 3), 613-27.
[3] Ingber, D. E. (1997). Tensegrity: The architectural basis of cellular mechanotransduction. Annual Review of Physiology, 59, 575-99
[4] Ingber, D. E. (2009), Keynote Speech, Dartmouth Medical School Class Day, June 13, 2009