Over 100 years ago skyscraper builder Louis Sullivan famously wrote,
It is the pervading law of all things organic and inorganic,
Of all things physical and metaphysical,
Of all things human and all things super-human,
Of all true manifestations of the head,
Of the heart, of the soul,
That the life is recognizable in its expression,
That form ever follows function. This is the law.
Sullivan got it half right. Though it is often the case that form follows function, at the cellular level, function follows form. At least, that is the finding of cell morphology studies, the field that analyzes cellular form. Such reports show that cells rely on their shape for all kinds of information, and a bad shape can mean a bad disease.
A recent publication on this theme is, "Mechanotransduction and epigenetic control in autoimmune diseases" by Gonzáleza et al. This Chilean team focused on epithelial cells. The epithelium is your slimy, gooey self, as opposed to your webby "connective" self, strong "muscular" self and brainy "nervous" self. These four types --epithelial, connective, muscular and nervous tissue--are the four classifications that account for each of the 100 quadrillion cells that make up your body.
The epithelial cells ooze important enzymes and participate in your sense of touch--if they stop working, you are very sick. The Chilean doctors proved that the epithelial cells that ooze spit (saliva, in medical terminology) from people with Sjögren's syndrome display different patterns of cell adhesion and shape.
Ingber pioneered many aspects of this type of study, and was the first to focus on tensegrity. Without tensegrity, you are left with other structural ideas, such as the inflated balloon, or a pile of bricks. Balloons and bricks, when stressed locally, show local deflection. Push a balloon and it dimples; push a brick and it either coheres with the other bricks are shears and falls off. A tensegrity, on the other hand, shows a global reaction and response--areas far from the area of pressure may contract. Ingber documents this global nature of cell morphology, in for example, a tensegrity fabric. You can see the video here: http://wyss.harvard.edu/viewmedia/26/retracting-tensegrity-fabric-
Note that the material simultaneously retracts throughout its entire depth. When the ECM adhesions of a spread, adherent cell are dislodged using trypsin, the cell, cytoplasm and nucleus all simultaneously retract as the cell rounds. A prestressed tensegrity fabric created from 36 interconnected tensegrity modules of the type shown in Fig. 1B that experiences a distending force at the top right corner; the other three corners are fixed. Notice that the entire material responds to the local force and that it exhibits undulating motion.
According to this approach, disease is not caused by invading bacteria, badly transcribed genes, or bad genes transcribed accurately. Instead, our focus turns to the mechanics of the cell, its beams and girders, though of course in cellular mechanics you won't find such gross structures-researchers look instead at molecules that mediate mechano-transductions, including the extracellular matrix (ECM) molecules, transmembrane integrin receptors (more on them in a moment), the intracellular cytoskeleton (CSK) structures, and their role in tissue regulation.
Ingber invented nano-scale magnetic twisting devices to test his ideas. The tiny manipulators can pinch specific integrins on a cell's surface. Integrins are prodded, since they are the cell's ECM sensors. Their manipulation has been found to be critical for regulation of cell growth, differentiation, tissue pattern and more. The ECM, via integrin receptors and other mechanisms, regulates cell and tissue morphogenesis by altering the structure of the CSK which, in turn, serves to orient much of the cell's metabolic machinery. Ingber has slowly built a body of evidence-based research measuring effects on CSK mechanics that result from independently varying cell-ECM contacts, cell shape, applied mechanical stresses, and the area over which forces are applied.
Being in good shape is no longer just an American English cliche for being in good health: these studies show that it is literally shape that determines whether your cells are healthy or diseased. Think about that when you stretch or slouch, have good posture or poor: tensegrity research shows, function follows form.
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