collagen and mechanical forces Biomechanics of the lung parenchyma: critical roles of

SUMMARY The connective tissue of the lung is not a static structure,even during normal functioning. The tissue is the end result ofa molecular hierarchical organization living in a dynamicbalance between continuous breakdown and remodeling that isalso modulated by mechanical forces. When this delicatedynamic balance is perturbed by external or internal chemicalchanges, such as those occurring in a disease process orenvironmental stimuli, the system dynamically remodels itselfby an excess or lack of producing or breaking up these largecomplex macromolecular structures. The result is a chemicallyand structurally different tissue with accordingly altered bio-mechanical properties. We have also argued that the changes inmatrix stiffness will alter the mechanical forces on the cells,which in turn may also influence the way cells remodel theinterstitium. An important consequence is that a completeunderstanding of tissue biomechanics and lung function willnot result solely from biochemical purification and biophysicalstudy of the molecules. Connective tissues must be studied asan integrated system within their natural biochemical andmechanical environments. Additionally, to fully appreciatehow diseases propagate spatially in the tissue and how theyprogress with time, it will be essential to map the regionalcorrelation between cell signaling, matrix composition, and thelocal biomechanical properties of the tissue.