The triphasic constitutive law [Lai, Hou and Mow (1991)] has been shown in some special 1D cases to successfully model the deformational and transport behaviors of charged-hydrated, porous-permeable, soft biological tissues, as typified by articular cartilage. Due to nonlinearities and other mathematical complexities of these equations, few problems for the deformation of such materials have ever been solved analytically. Using a perturbation procedure, we have linearized the triphasic equations with respect to a small imposed axial compressive strain, and obtained an equilibrium solution, as well as a short-time boundary layer solution for the mechano-electrochemical (MEC) fields for such a material under a 2D unconfined compression test. The present results show that the key physical parameter determining the deformational behaviors is the ratio of the perturbation of osmotic pressure to elastic stress, which leads to changes of the measurable elastic coefficients. From the short-time boundary layer solution, both the lateral expansion and the applied load are found to decrease with the square root of time. The predicted deformations, flow fields and stresses are consistent with the analysis of the short time and equilibrium biphasic (i.e., the solid matrix has no attached electric charges) [Armstrong, Lai and Mow (1984)]. These results provide a better understanding of the manner in which fixed electric charges and mobile ions within the tissue contribute to the observed material responses.
This article is a summary of a lecture presented at a symposium on "Mechanics and Chemistry of Biosystems" in honor of Professor Y.C. Fung that convened at the University of California, Irvine in February 2004. The article reviews work from our laboratory that focuses on the mechanism by which mechanical and chemical signals interplay to control how individual cells decide whether to grow, differentiate, move, or die, and thereby promote pattern formation during tissue morphogenesis. Pursuit of this challenge has required development and application of new microtechnologies, theoretical formulations, computational models and bioinformatics tools. These approaches have been used to apply controlled mechanical stresses to specific cell surface molecules and to measure mechanical and biochemical responses; to control cell shape independently of chemical factors; and to handle the structural, hierarchical and informational complexity of living cells. Results of these studies have changed our view of how cells and tissues control their shape and mechanical properties, and have led to the discovery that integrins and the cytoskeleton play a central role in cellular mechanotransduction. Recognition of these critical links between mechanics and cellular biochemistry should lead to novel strategies for the development of new drugs and engineered tissues, as well as biomimetic microdevices and nanotechnologies that more effectively function within the context of living tissues.
Vertically aligned multi-walled carbon nanotubes (MWCNTs) have been reported in fabricating nanoelectrode arrays. Further studies on optimizing this system for the development of ultrasensitive DNA sensors are reported here. The mechanical stability of the as-grown MWCNT array can be improved by polymer coating or SiO2 encapsulation. The latter method provides excellent electronic and ionic insulation to the sidewall of MWCNTs and the underlying metal layer, which is investigated with electrochemical impedance spectroscopy. The insulation ensures well-defined nanoelectrode behavior. A method is developed for selectively functionalizing biomolecules at the open end of MWCNTs while keeping the SiO2 surface passivated, using the unique graphitic chemistry. An ultrahigh sensitivity approaching the limit of fluorescence techniques is obtained with this system for DNA detection.
The ability to detect, localize, quantify and monitor the expression of specific genes in living cells in real-time will offer unprecedented opportunities for advancement in molecular biology, disease pathophysiology, drug discovery, and medical diagnostics. However, current methods for quantifying gene expression employ either selective amplification (as in PCR) or saturation binding followed by removal of the excess probes (as in microarrays and in situ hybridization) to achieve specificity. Neither approach is applicable when detecting gene transcripts within living cells. Here we review the recent development in engineering nanostructured molecular probes for gene detection in vivo, describe probe design approaches and its structure-function relations, and discuss the critical issues and challenges in performing living cell gene detection with high specificity, sensitivity and signal-to-background ratio. The underlying biological and biochemical aspects are illustrated.