{"title":"Engineering nanostructured probes for sensitive intracellular gene detection.","authors":"G. Bao, A. Tsourkas, P. Santangelo","doi":"10.3970/MCB.2004.001.023","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.023","url":null,"abstract":"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.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 1 1","pages":"23-36"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70238710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Y.C. \"Bert\" Fung: the father of modern biomechanics.","authors":"Ghassan S Kassab","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 1","pages":"5-22"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26097515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huajian Gao, Baohua Ji, Markus J Buehler, Haimin Yao
{"title":"Flaw tolerant bulk and surface nanostructures of biological systems.","authors":"Huajian Gao, Baohua Ji, Markus J Buehler, Haimin Yao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bone-like biological materials have achieved superior mechanical properties through hierarchical composite structures of mineral and protein. Gecko and many insects have evolved hierarchical surface structures to achieve extraordinary adhesion capabilities. We show that the nanometer scale plays a key role in allowing these biological systems to achieve their superior properties. We suggest that the principle of flaw tolerance may have had an overarching influence on the evolution of the bulk nanostructure of bone-like materials and the surface nanostructure of gecko-like animal species. We demonstrate that the nanoscale sizes allow the mineral nanoparticles in bone to achieve optimum fracture strength and the spatula nanoprotrusions in Gecko to achieve optimum adhesion strength. In both systems, strength optimization is achieved by restricting the characteristic dimension of the basic structure components to nanometer scale so that crack-like flaws do not propagate to break the desired structural link. Continuum modeling and atomistic simulations have been conducted to verify the concept of flaw tolerance at nanoscale. A simple tension-shear chain model has been developed to model the stiffness and fracture energy of biocomposites. It is found that, while the problem of low toughness of mineral crystals is alleviated by restricting the crystal size to nanoscale, the problem of low modulus of protein has been solved by adopting a large aspect ratio for the mineral platelets. The fracture energy of biocomposites is found to be proportional to the effective shear strain and the effective shear stress in protein along its path of deformation to fracture. The bioengineered mineral-protein composites are ideally suited for fracture energy dissipation as the winding paths of protein domain unfolding and slipping along protein-mineral interfaces lead to very large effective strain before fracture. The usual entropic elasticity of biopolymers may involve relatively small effective stress and may not be able to ensure simultaneous domain unfolding and interface slipping. Cross-linking mechanisms such as Ca++ induced sacrificial bonds in bone can increase the shear stress in protein and along the protein-mineral interface, effectively converting the behavior of entropic elasticity to one that resembles metal plasticity. The sacrificial bond mechanism not only builds up a large effective stress in protein but also allows protein deformation and interface slipping to occur simultaneously under similar stress levels, making it possible to engineer a very long range of deformation under significant stress in order to maximize energy absorption. Optimization of mineral platelets near theoretical strength is found to be crucial for allowing a large effective stress to be built up in protein via cross-linking mechanisms such as Ca++ induced sacrificial bonds. Similarly, for gecko adhesion, the strength optimization of individual spatulas is found to play a ","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 1","pages":"37-52"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26095251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Yuan-Cheng Fung: A scientific giant and a kind man.","authors":"Pin Tong","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26097514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cantilever arrays for multiplexed mechanical analysis of biomolecular reactions.","authors":"Min Yue, J. Stachowiak, A. Majumdar","doi":"10.3970/MCB.2004.001.211","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.211","url":null,"abstract":"Microchips containing arrays of cantilever beams have been used to mechanically detect and quantitatively analyze multiple reactions of DNA hybridization and antigen-antibody binding simultaneously. The reaction-induced deflection of a cantilever beam reflects the interplay between strain energy increase of the beam and the free energy reduction of a reaction, providing an ideal tool for investigating the connection between mechanics and chemistry of biomolecular reactions. Since free energy reduction is common for all reactions, the cantilever array forms a universal platform for label-free detection of various specific biomolecular reactions. A few such reactions and their implications in biology and biotechnology are discussed.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3 1","pages":"211-20"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70239931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Stochastic Analysis of a Brownian Ratchet Model for Actin-Based Motility and Integrate-and-Firing Neurons","authors":"H. Qian","doi":"10.3970/mcb.2004.001.267","DOIUrl":"https://doi.org/10.3970/mcb.2004.001.267","url":null,"abstract":"In recent single-particle tracking (SPT) measurements on {it Listeria monocytogenes} motility {em in vitro}, the actin-based stochastic dynamics of the bacterium movement is analyzed statistically (Kuo and McGrath, 2000). The mean-square displacement (MSD) of the detrended trajectory exhibit a linear behavior; it has been suggested that a corresponding analysis for the Brownian ratchet model (Peskin, Odell, & Oster, 1993) leads to a non-monotonic MSD. A simplified version of the Brownian ratchet, when its motion is limited by the bacterium movement, is proposed and analyzed stochastically. Analytical results for the simple model are obtained and statistical data analysis is investigated. The MSD of the stochastic bacterium movement is a quadratic function while the MSD for the detrended trajectory is shown to be linear. The mean velocity and effective diffusion constant of the propelled bacterium in the long-time limit, and the short-time relaxation are obtained from the MSD analysis. The MSD of the gap between actin and the bacterium exhibits an oscillatory behavior when there is a large resistant force from the bacterium. The stochastic model for actin-based motility is also mathematically equivalent to a model for integrate-and-firing neurons. Hence our mathematical results have applications in other biological problems. For comparison, a continuous formalism of the BR model with great analytical simplicity is also studied.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"13 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2001-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70240399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}