Tensegrity and Mechanoregulation: From Skeleton to Cytoskeleton

Christopher S. Chen and Donald E. Ingber, Children’s Hospital and Harvard Medical School. Osteoarthritis and Cartilage (1999) 7, 81-94. doi:10.1053/joca.1998.1064

“In living organisms, use of a hierarchy of tensegrity networks both optimizes structural efficiency and provides a mechanism to mechanically couple the parts with the whole: mechanical stresses applied at the macroscale result in structural rearrangements at the cell and molecular level.”

“…mechano-responsiveness is actually a fundamental feature of all living tissues. Experiments with cultured cells confirm that mechanical stresses can directly alter many cellular processes, including signal transduction, gene expression, growth, differentiation, and survival.”

One concept discussed is tensegrity: structures containing both tension and compression elements:
“The compression resistant bones of the ‘skeleton’ are smaller subunits within a larger supporting framework, or ‘musculoskeletal system’, that is comprised of an interconnected network of bones, ligaments, tendons, muscles and cartilage….. Through use of this sort of interconnected framework of tension and compression elements, we optimize structural efficiency without sacrificing the ability of the structure to withstand a variety of structural requirements such as torsion and bending as well as tension and compression demanded of our bodies.”

Christopher S. Chen and Donald E. Ingber, Children’s Hospital and Harvard Medical School. Osteoarthritis and Cartilage (1999) 7, 81-94. doi:10.1053/joca.1998.1064

The Concept of Prestress:

Prestressing means the intentional creation of permanent stresses in a structure for the purpose of improving its performance under various service conditions. There are the following basic types of prestressing:

Precompression (mostly, with the weight of the structure itself)
Pretensioning with high-strength embedded tendons
Post-tensioning with high-strength bonded or unbonded tendons

Chen and Ingber discuss prestress in articular joints:

“The stable position of the bones that articulate at any joint depends on the tensile forces of the muscles, tendons, and ligaments that bridge them. In the knee, for example, the cartilaginous regions at the end of apposing bones come into direct contact due to compression. Most of this compression is not due to gravity, rather it is created by the surrounding ligaments and tendons that cross the joint, and these are always under tension. The internal tension and/or pre-stress in this system stabilizes the joint….”

“To understand the critical importance of these internal tensions and/or pre-stress in this complex structure, one only needs to examine the case where tendons and ligaments loosen: this results in joint instability, increased wear on the articular cartilage, pain and loss of function.”

“Tensegrity and mechanoregulation: from skeleton to cytoskeleton”, Christopher S. Chen and Donald E. Ingber, Children’s Hospital and Harvard Medical School. Osteoarthritis and Cartilage (1999) 7, 81-94. doi:10.1053/joca.1998.1064

Wolff’s law: A law according to which biologic systems such as hard and soft tissues become distorted in direct correlation to the amount of stress imposed upon them.

Chen and Ingber discuss Wolff’s law and use the femur as an example and point out that the bony trabeculae that make up the cancellous bone in the medial and lateral sides of the femur have different structure due to the different localized forces upon them.

“This observation suggests that the living cells that continually remodel bone are able to sense changes in mechanical stresses in their local environment and that they respond by depositing new Extracellular Matrix (ECM) where it is needed and remove it from where it is not.”

“Architectural organization on yet a smaller size scale (the molecular level) also contributes to the mechanical strength of biological tissue. In the bone, the matrix of each trabeculum consists of a composite material containing hydroxyapatite crystals embedded within a network of collagen fibrils. The collagen augments the tensile strength of the bone, while the minerals contribute largely to its compressive stiffness and strength. In the living organism, the stress in the bone ECM is influenced by the shape of the entire bone, the pull of the surrounding muscles and tendons, and its loading conditions.”

And besides bone, what about the soft tissues:

“Pre-stress also plays an important role in determining the mechanics of cartilage, tendons, and ligaments. In cartilage, the loose collagen network is stretched open and pre-stressed by the osmotic force of hydration of embedded proteoglycan molecules, however, the cellular components (chondrocytes) and their internal support elements (cytoskeleton, nucleus) may also bear some mechanical loads. In soft tissues that are composed mostly of parallel collagen fibers and elastin, such as ligaments and tendons, the pre-stress results from the active contraction of living cells (myofibroblasts) that are embedded within its ECM.”

Before I start the modern thoughts on cellular level mechanics, another quote/incite from Dr. Still:

Philosophy of Osteopathy, Andrew Taylor Still, originally published 1899, chapter 10, pg. 73.

“The fascia gives one of, if not the greatest problems to solve as to the part it takes in life and death. It belts each muscle, vein, nerve and all organs of the body. It is almost a network of nerves, cells and tubes, running to and from it; it is crossed and filled with, no doubt, millions of nerve centers and fibers to carry on the work of secreting and excreting fluid vital and destructive. By its action we live, and by its failure we shrink, or swell, and die. Each muscle plays its part in active life. Each fiber of all muscles owes its pliability to that yielding septum-washer, that gives all muscles help to glide over and around all adjacent muscles and ligaments, without friction or jar. It not only lubricates the fibers but gives nourishment to all parts of the body. Its nerves are so abundant that no atom of flesh fails to get nerve and fluid supply there from.”

“This life is surely too short to solve the uses of the fascia in animal forms. It penetrates even its own finest fibers to supply and assist its gliding elasticity. Just a thought of the completeness and universality in all parts, even though you turn the vision of your mind to follow the infinitely fine nerves. There you see the fascia, and in your wonder and surprise, you exclaim, ‘Omnipresent in man and all other living beings of the land and sea.’ Other great questions come to haunt the mind with joy and admiration, and we can see all the beauties of life and exhibition by that great power with which the fascia is endowed. The soul of man with all the streams of pure living water seems to dwell in the fascia of his body.”

“Most conventional engineering models of living cells assume external forces are distributed evenly across the cell surface and consider the key load-bearing elements of the cell to be a homogeneous, isotropic viscous fluid cytosol or homogenous, isotropic viscoelastic solid cytoskeleton, and surrounding tensed membrane. In reality, we find that the cells within a living tissue, such as a tensed ligament are not evenly glued to their underlying ECM adhesive substrate, but instead, actually anchor themselves to ECM through spot weld-like attachments that are known as ‘focal adhesions’.

“These sites are where cells pull together or cluster multiple transmembrane receptors, known as ‘integrins’, that bind to specific ECM molecules on the outside of the cell and thereby mediate cell anchorage. Surrounding regions of the plasma membrane lack these receptors and do not mechanically connect to the ECM scaffold.”

“Importantly, all living cells are contractile: they generate tension within their internal cytoskeleton via an actomyosin filament sliding mechanism similar to that used in muscle.”

“Quantitative analysis of the mechanical properties of the cytoplasm and nucleus have confirmed that structural interplay in the cytoskeleton is complex and that the behaviors of these different filament systems are not simply additive. Actin microfilaments form a volume filling gel that can bear compression, but cannot effectively resist external tension and they tear at high tensile strains. The intermediate filament network is itself poor at resisting lateral compression, yet it efficiently resists tension and hardens at high strains.

However, when these two filament systems are combined in living cells, a fiber-reinforced composite material is formed that can provide both load-bearing functions with greater efficiency, just as many biologic tissues with hierarchical structural arrangements. For cells, however, full mechanical responsiveness and structural stability requires the added presence of microtubules to locally resist the inward contraction of the surrounding tensile cytoskeleton and thereby, to impose a pre-stress in this interconnected molecular network.”

“Recent studies have confirmed that living cells and nuclei are literally ‘hard-wired’ such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating micropipettes bound to cell surface integrins (and the focal adhesion), cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the

applied tension field in time periods much faster than those required for polymerization. Thus, while the cytoskeleton is surrounded by lipid membranes and penetrated by viscous cytosol, it is the discrete filamentous cytoskeleton that provides the main path for mechanical signal transfer through the cytoplasm. The efficiency of force transfer depends directly on the mechanical properties of the cytoskeleton which, in turn, are governed by various interactions between microfilaments, intermediate filaments, and microtubules acting in the cytoplasm.”

:“Tensegrity and mechanoregulation: from skeleton to cytoskeleton”, Christopher S. Chen and Donald E. Ingber, Children’s Hospital and Harvard Medical School. Osteoarthritis and Cartilage (1999) 7, 81-94. doi:10.1053/joca.1998.1064

This final quote from doctors Chen and Ingber drives home the point that research in the field of tensegrity and mechanical signaling is showing that mechanical manipulation of the tissues is having an effect not only on the gross anatomical structures, but also deep into the cellular and genetic signals:

“The demonstration of discrete mechanical linkages between cells and their ECM via integrins also suggests how mechanical signals resulting from ECM deformation may be transferred across cell surface integrin receptors to distinct structures in the cell and nucleus, including ion channels, nuclear pores, nucleoli, chromosomes, and perhaps even individual genes, independently of ongoing chemical signaling mechanisms. In fact, recent studies have demonstrated that signal transduction pathways can be activated within milliseconds after cell surface integrins and associated cytoskeletal connections are mechanically stressed, but not when unanchored cell surface transmembrane receptors are similarly perturbed on the same cells. This type of physical coupling between intracellular structures, cell surface receptors, and the ECM could serve to coordinate, complement and constrain slower diffusion-based chemical signaling pathways and thus, explain how mechanical distortion of ECM caused by gravity or other mechanical stresses can change cell shape, alter nuclear functions, and switch cells between different genetic programs.”