Abstract-A comprehensive computational study was undertaken to identify the extent to which elastoplastic properties of ductile materials could be determined from instrumented sharp indentation and to quantify the sensitivity of such extracted properties to variations in the measured indentation data. Large deformation finite element computations were carried out for 76 different combinations of elasto-plastic properties that encompass the wide range of parameters commonly found in pure and alloyed engineering metals: Young's modulus, E, was varied from 10 to 210 GPa, yield strength, s y , from 30 to 3000 MPa, and strain hardening exponent, n, from 0 to 0.5, and the Poisson's ratio, n, was fixed at 0.3. Using dimensional analysis, a new set of dimensionless functions were constructed to characterize instrumented sharp indentation. From these functions and elasto-plastic finite element computations, analytical expressions were derived to relate indentation data to elasto-plastic properties. Forward and reverse analysis algorithms were thus established; the forward algorithms allow for the calculation of a unique indentation response for a given set of elasto-plastic properties, whereas the reverse algorithms enable the extraction of elasto-plastic properties from a given set of indentation data. A representative plastic strain e r was identified as a strain level which allows for the construction of a dimensionless description of indentation loading response, independent of strain hardening exponent n. The proposed reverse analysis provides a unique solution of the reduced Young's modulus E*, a representative stress s r , and the hardness p ave . These values are somewhat sensitive to the experimental scatter and/or error commonly seen in instrumented indentation. With this information, values of s y and n can be determined for the majority of cases considered here, provided that the assumption of power law hardening adequately represents the full uniaxial stress-strain response. These plastic properties, however, are very strongly influenced by even small variations in the parameters extracted from instrumented indentation experiments. Comprehensive sensitivity analyses were carried out for both forward and reverse algorithms, and the computational results were compared with experimental data for two materials. 

Strengthening materials traditionally involves the controlled creation of internal defects and boundaries so as to obstruct dislocation motion. Such strategies invariably compromise ductility, the ability of the material to deform, stretch, or change shape permanently without breaking. Here, we outline an approach to optimize strength and ductility by identifying three essential structural characteristics for boundaries: coherency with surrounding matrix, thermal and mechanical stability, and smallest feature size finer than 100 nanometers. We assess current understanding of strengthening and propose a methodology for engineering coherent, nanoscale internal boundaries, specifically those involving nanoscale twin boundaries. Additionally, we discuss perspectives on strengthening and preserving ductility, along with potential applications for improving failure tolerance, electrical conductivity, and resistance to electromigration.

Recent advances in nanotechnology have stimulated novel applications in biomedicine where nanoparticles (NPs) are used to achieve drug delivery and photodynamic therapy. In chemotherapeutic cancer treatment, tumor-specific drug delivery is a topic of considerable research interest for achieving enhanced therapeutic efficacy and for mitigating adverse side effects. Most anticancer agents are incapable of distinguishing between benign and malignant cells, and consequently cause systematic toxicity during cancer treatment. Owing to their small size, ligand-coated NPs can be efficiently directed toward, and subsequently internalized by tumor cells through ligand-receptor recognition and interaction (see Fig. 1), thereby offering an effective approach for specific targeting of tumor cells. For example, branching dendrimers have recently been identified as potential candidates for site-specific drug carriers.[2] NPs have also been exploited in other biomedical applications such as bioimaging [3,4] and biosensing. [5,6] It has been demonstrated that florescent quantum dots are efficient in tumor cell imaging, recognition, and tracking, [3,4] and that gold NPs are capable of detecting small proteins. [5,6] To enable rational design of such NP-based agents, it is essential to understand the underlying mechanisms that govern the transmembrane transport and invagination of NPs in biological cells. In this communication, we present a thermodynamic model for receptormediated endocytosis of ligand-coated NPs. We identify an optimal NP radius at which the cellular uptake reaches a maximum of several thousand at physiologically relevant parameters, and we show that the cellular uptake of NPs is regulated by membrane tension, and can be elaborately controlled by particle size. The optimal NP radius for endocytosis is on the order of 25−30 nm, which is in good agreement with prior estimates. [7] Theoretical models [7−11] have provided insights into the dynamics of receptor-mediated endocytosis based on energetic and kinetic considerations, primarily in the context of virus budding. Lerner et al.[8] argued that the discreteness of membrane wrapping via ligandreceptor binding results in a corrugated energy landscape for NP wrapping, which governs the kinetics of endocytosis. In contrast, Gao et al. [7] proposed that the endocytic rate is limited by

The past decade has seen substantial growth in research into how changes in the biomechanical and biophysical properties of cells and subcellular structures influence, and are influenced by, the onset and progression of human diseases. This paper presents an overview of the rapidly expanding, nascent field of research that deals with the biomechanics and biophysics of cancer cells. The review begins with some key observations on the biology of cancer cells and on the role of actin microfilaments, intermediate filaments and microtubule biopolymer cytoskeletal components in influencing cell mechanics, locomotion, differentiation and neoplastic transformation. In order to set the scene for mechanistic discussions of the connections among alterations to subcellular structures, attendant changes in cell deformability, cytoadherence, migration, invasion and tumor metastasis, a survey is presented of the various quantitative mechanical and physical assays to extract the elastic and viscoelastic deformability of cancer cells. Results available in the literature on cell mechanics for different types of cancer are then reviewed. Representative case studies are presented next to illustrate how chemically induced cytoskeletal changes, biomechanical responses and signals from the intracellular regions act in concert with the chemomechanical environment of the extracellular matrix and the molecular tumorigenic signaling pathways to effect malignant transformations. Results are presented to illustrate how changes to cytoskeletal architecture induced by cancer drugs and chemotherapy regimens can significantly influence cell mechanics and disease state. It is reasoned through experimental evidence that greater understanding of the mechanics of cancer cell deformability and its interactions with the extracellular physical, chemical and biological environments offers enormous potential for significant new developments in disease diagnostics, prophylactics, therapeutics and drug efficacy assays.