Effects Of Matrix Viscoelasticity On HepG2Metastasis With A Novel Microfiuidic Device

Cancer metastasis is a complex dynamic cascade with multi-step process, which isinfluenced by kinds of biochemical and biophysical factors of the microenvironment,changing with time and space. It is the cause of death of more than90%of cancerpatients.Matrix mechanics, an important micro-environmental factor, has attracted muchattention, especially the stiffness of substrate. The studies has been made in themechanics of extracellular matrix cancer during metastasis show that the mechanicalproperties of the matrix played as important role in cancer metastasis process asbiochemical factors. The stiffness of substrate has been considered as one of the mostimportant factors for appropriate physiological function in numerous contexts in thepast decades. In fact, the extracellular matrix (ECM) around the cell is a kind ofmaterial with viscoelasticity. Besides the "soft-stiffness" concept in the usual sense, theviscosity component of the ECM, which is used for describing the loss part of energyduring interaction with the cell, is bound to have impact on the migration of the cancercell. But the role of which playing in the cascade of events of cancer metastasis ispoorly understood. And during the early research, cells are cultured on the2D plane butnot a dimensional space, which is different from the microenvironment of cancer cellsin vivo.To investigate the influence of ECM viscoelasticity on the cascade of events ofcancer metastasis in a microenvironment approximately in vivo which can afford cancercell an in vivo-like pathophysiologic3D microenvironments, we modified amicrofluidic device, according to the work of Carlos P. Huang et el, to establish a3Dmetastasis research model by precisely patterning tumor cells and ECM in microfluidicchannels. The viscoelasticity of collagen gel was controlled by variable gelconcentrations, measured by rheometer, the effect of which on viability, cytoskeleton,invasion and migration of HepG2were investigated. The results revealed that within thescope of this research expedition the viscoelasticity of collagen gels increased with theincrease of concentration; the viability decreased as the increase of viscoelasticity, thecytoskeleton seems denser in the collagen with high viscoelasticity, the invasion andmigration rate decreased as the increase of viscoelasticity.The results suggested that the microfluidic device fabricated as a metastasis model could provide an in vivo-like pathophysiologic microenvironment for cancer cells tomaintain and monitor the response of cancer cell to the change of their environments inreal time. And those results also suggested that the viscoelasticity of collagen gels,mainly the elasticity, play a role in the viability, the cytoskeleton, the capacity and rateof invasion and migration of hepG2.