During the past 2½ decades, novel research techniques have been developed to study cellular mechanics.
52 With these new techniques, Ingber and others have convincingly demonstrated that cells adhere to the mechanical principles of tensegrity architecture
9,10,12 and have confirmed the prestressed nature of living cells.
14,15,52-56 This cellular prestress allows the cell to respond to changing external forces by transmitting the forces throughout the cell, consistent with tensegrity architectural principles. Further, when cells are attached to a flexible extracellular substrate, they pull on the substrate and cause it to wrinkle, demonstrating the transfer of prestress within the cell to the extracellular environment.
8,17
After Ingber and others established that cells are prestressed, the next step was to identify the tension-producing and compression-resisting elements within the cell. Initial evidence in the late 1980s and early 1990s compared in vitro biophysical properties of intracellular cytoskeletal components with in vivo immunohistochemical analysis of the cytoskeletal elements.
9 In vitro, isolated microfilaments (actin stress fibers) appear entangled like a nontensed rope lying on the ground, while hollow microtubules appear straight like a rod or beam. In vivo, microfilaments appear completely straight like a tensed rope and form triangulated geodesic networks within the cell, while microtubules appear bent like a tree bending in the wind.
9 Consistent with established engineering principles (ie, tension straightens, compression bends), these observations indicated that microfilaments function as tension elements and microtubules function as discontinuous compression elements within the cell (
Figure 3).
9 However, direct evidence was still needed. For microfilaments, the direct evidence was provided in 2006 with the use of laser nanoscissor technology that cut microfilaments in living prestressed cells.
56 After disruption with a laser, microfilaments spontaneously recoiled.
56 Additional studies
15,57 supported the theory that microtubules are compression resistant struts inside the cell but suggested that the ECM is also involved in resisting cellular tension. Studies
17,53 in the twenty-first century have now confirmed that cells are linked to the ECM and that the ECM plays a pivotal role in resisting tensional forces of cells in addition to microtubules. The establishment of a dynamic biophysical connection between cells and their surrounding ECM introduced the possibility of a tensegrity-based hierarchical organization of biological organisms.
A tensegrity model of a cell with a separate tensegrity nucleus intimately connected to the larger tensegrity cell was introduced in Ingber's original 1985 publication on cellular tensegrity.
48 The model predicts that any force applied to the cell will be transmitted throughout the cell and also to the nucleus, which is itself a tensegrity structure (
Figure 4). During the past decade, studies
34,49 on cultured cells have confirmed that a direct connection from the ECM through the cytoskeleton and down to the nucleus exists and that mechanical forces applied to ECM components are transmitted directly to the cell and nucleus as predicted in hierarchical tensegrity models. The specific link from the ECM to the cell cytoskeleton occurs by means of integrins (transmembrane proteins) clustered together to form focal adhesion complexes, which couple proteins of the ECM to the microtubules and microfilaments that form the cytoskeletal tensegrity system.
58 Focal adhesion complexes can be thought of as points of integration between tension elements and compression elements at the cellular biotensegrity level (
Figure 3). In addition, intermediate filaments (rope-like fibers composed of various proteins depending on the given cell type, which function as tension elements) provide a direct connection from focal adhesion complexes to the nucleus.
50 Taken together, cellular experiments provide convincing evidence of at least a 3-tiered hierarchical organization of biological life (ECM ↔ cell ↔ nucleus).
This hierarchical organization has also been supported by whole tissue experiments. For the past decade, neurologist Helene Langevin, MD, has been using in vivo and ex vivo tissue stretch experiments on mouse superficial fascia (subcutaneous areolar tissue) to study fibroblast physiology. Langevin et al
59 demonstrated that mouse fibroblasts are intimately connected to their ECM in superficial fascia and spread out in a sheet-like fashion when mechanically stretched both in vivo and ex vivo. Further, Langevin coauthored a report on an increase in the cross-sectional area of the nucleus and a decrease in the number of nuclear membrane invaginations occurring in fibroblasts during ex vivo stretch of mouse superficial fascia.
60 These results support the findings in cell culture experiments, demonstrating the presence of a true hierarchical organization of biological tissues.
Complementing these laboratory experiments, mathematical modeling of tensegrity systems has been shown to predict numerous aspects of cellular dynamics.
13,61 In addition, biomedical engineers are using tensegrity-based models of red blood cells to begin to understand the cells' ability to constantly deform in circulation while preserving their underlying shape.
62 Further, when modeling individual components of the cellular tensegrity system, researchers discovered that tensegrity models of microfilaments (actin-myosin stress fibers) predict several of their mechanical properties observed in situ.
63 This research further strengthens the biotensegrity principle of hierarchical organization of biological organisms—systems within systems within systems—by demonstrating how a component of a tensegrity system is itself a tensegrity system.
Research on cellular tensegrity has greatly advanced our understanding of cell biology. By viewing the cell as a tensegrity system, scientists can now explain complex behaviors of living cells and understand how cells adapt to their ever-changing mechanical environment. Further, scientists can begin to explain how prestressed cells, linked to the ECM and other cells in hierarchical systems, can convert dynamic mechanical information into biochemical changes through the process of mechanotransduction. Research at the cellular level has provided the backbone upon which application of tensegrity architecture can be applied to all size scales of biological organisms, advancing the concept of biotensegrity.