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A major challenge in studying tumor cell invasion into its surrounding tissue is to identify the contribution of individual factors in the tumor microenvironment (TME) to the process. One of the important elements of the TME is the fibrous extracellular matrix (ECM) which is known to influence cancer cell invasion, but exactly how remains unclear. Therefore, there is a need for new models to unravel mechanisms behind the tumor-ECM interaction. In this article, we present a new microfabrication method, called selective curing, to integrate ECM-mimicking layers between two microfluidic channels. This method enables us to study the effect of 3D matrices with controlled architecture, beyond the conventionally used hydrogels, on cancer invasion in a controlled environment. As a proof of principle, we have integrated two el e c trospun Polycaprolactone (PCL) matrices with different fiber diameters in one chip. We then studied the 3D migration of MDA-MB-231 breast cancer cells into the matrices under the influence of a chemotactic gradient. The results show that neither the invasion distance nor the general cell morphology is affected significantly by the difference in fiber size of these matrices. The cells however do produce longer and more protrusions in the matrix with smaller fiber size. This microfluidic system enables us to study the influence of other factors in the TME on cancer development as well as other biological applications as it provides a controlled compartmentalized environment compatible with cell culturing. [ABSTRACT FROM AUTHOR]

Flat-tip micro-indentation tests were performed on quenched and annealed polymer glasses at various loading speeds. The results were analyzed using an elasto-viscoplastic constitutive model that captures the intrinsic deformation characteristics of a polymer glass: a strain-rate dependent yield stress, strain softening and strain hardening. The advantage of this model is that changes in yield stress due to physical aging are captured in a single parameter. The two materials studied (polycarbonate (PC) and poly(methyl methacrylate) (PMMA)) were both selected for the specific rate-dependence of the yield stress that they display at room temperature. Within the range of strain rates experimentally covered, the yield stress of PC increases linearly with the logarithm of strain rate, whereas, for PMMA, a characteristic change in slope can be observed at higher strain rates. We demonstrate that, given the proper definition of the viscosity function, the flat-tip indentation response at different indentation speeds can be described accurately for both materials. Moreover, it is shown that the model captures the mechanical response on the microscopic scale (indentation) as well as on the macroscopic scale with the same parameter set. This offers promising possibilities of extracting mechanical properties of polymer glasses directly from indentation experiments. [ABSTRACT FROM AUTHOR]

This paper describes the development of the contact area during indentation of polycarbonate. The contact area was measured in situ using an instrumented indentation microscope and compared with numerical simulations using an elasto-plastic constitutive model. The parameters in the model were obtained using macroscopic tests. Indentations were performed on samples with different thermal histories and at different speeds. For all cases, the numerical model correctly predicted the development of the contact area during indentation. For increasing strain rates, the contact area decreased at equal indentation depths. Annealing the samples resulted in a smaller contact area at equal indentation depth. Using only numerical simulation, it was also shown that pile-up around the indenter resulted from localization effects and was, thus, promoted by strain-softening properties of the indented material. Strain hardening, on the other hand, will tend to promote sink-in. Finally, we performed simulations of load relaxation during indentation. The results indicate that about 40% of the total observed relaxation may be assigned to plastic effects. [ABSTRACT FROM AUTHOR]