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David C. Lin

Bio: David C. Lin is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Indentation & Nanoindentation. The author has an hindex of 7, co-authored 12 publications receiving 895 citations.

Papers
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Journal ArticleDOI
TL;DR: This paper compiled a series of synergistic strategies into an algorithm that overcomes many of the complications that have previously impeded efforts to automate the fitting of contact mechanics models to indentation data, and allows for improved consistency and minimized user intervention.
Abstract: The atomic force microscope (AFM) has found wide applicability as a nanoindentation tool to measure local elastic properties of soft materials. An automated approach to the processing of AFM indentation data, namely, the extraction of Young's modulus, is essential to realizing the high-throughput potential of the instrument as an elasticity probe for typical soft materials that exhibit inhomogeneity at microscopic scales. This paper focuses on Hertzian analysis techniques, which are applicable to linear elastic indentation. We compiled a series of synergistic strategies into an algorithm that overcomes many of the complications that have previously impeded efforts to automate the fitting of contact mechanics models to indentation data. AFM raster data sets containing up to 1024 individual force-displacement curves and macroscopic compression data were obtained from testing polyvinyl alcohol gels of known composition. Local elastic properties of tissue-engineered cartilage were also measured by the AFM. All AFM data sets were processed using customized software based on the algorithm, and the extracted values of Young's modulus were compared to those obtained by macroscopic testing. Accuracy of the technique was verified by the good agreement between values of Young's modulus obtained by AFM and by direct compression of the synthetic gels. Validation of robustness was achieved by successfully fitting the vastly different types of force curves generated from the indentation of tissue-engineered cartilage. For AFM indentation data that are amenable to Hertzian analysis, the method presented here minimizes subjectivity in preprocessing and allows for improved consistency and minimized user intervention. Automated, large-scale analysis of indentation data holds tremendous potential in bioengineering applications, such as high-resolution elasticity mapping of natural and artificial tissues.

296 citations

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TL;DR: Although this finding supports the generally accepted view that many soft materials can be assumed to be linear elastic at small deformations, the nonlinear models facilitate analysis of intrinsically nonlinear tissues and large-strain indentation behavior.
Abstract: The lack of practicable nonlinear elastic contact models frequently compels the inappropriate use of Hertzian models in analyzing indentation data and likely contributes to inconsistencies associated with the results of biological atomic force microscopy measurements. We derived and validated with the aid of the finite element method force-indentation relations based on a number of hyperelastic strain energy functions. The models were applied to existing data from indentation, using microspheres as indenters, of synthetic rubber-like gels, native mouse cartilage tissue, and engineered cartilage. For the biological tissues, the Fung and single-term Ogden models achieved the best fits of the data while all tested hyperelastic models produced good fits for the synthetic gels. The Hertz model proved to be acceptable for the synthetic gels at small deformations (strain < 0.05 for the samples tested), but not for the biological tissues. Although this finding supports the generally accepted view that many soft materials can be assumed to be linear elastic at small deformations, the nonlinear models facilitate analysis of intrinsically nonlinear tissues and large-strain indentation behavior.

256 citations

Journal ArticleDOI
TL;DR: This work surveys recent progress in the application of nanoindentation to characterize the local mechanical properties of polymer gels and biological tissues and stresses the need for contact mechanics models that more accurately represent the large-strain behaviour of soft matter.
Abstract: We survey recent progress in the application of nanoindentation to characterize the local mechanical properties of polymer gels and biological tissues. We review the theories, analytical models based thereon, and data processing techniques commonly used to determine elastic properties of these classes of materials by instrumented nanoindentation. Examples from the testing of synthetic and biological gels are used to illustrate the limitations of existing theories and approaches. Emphasis is placed on the need for contact mechanics models that more accurately represent the large-strain behaviour of soft matter.

165 citations

Journal ArticleDOI
TL;DR: The authors' comprehensive algorithm for automated extraction of Young's moduli from AFM indentation data has been expanded to recognize the presence of either adhesive or Hertzian behavior and apply the appropriate contact model.
Abstract: In the first of this two-part discourse on the extraction of elastic properties from atomic force microscopy (AFM) data, a scheme for automating the analysis of force-distance curves was introduced and experimentally validated for the Hertzian (i.e., linearly elastic and noninteractive probe-sample pairs) indentation of soft, inhomogeneous materials. In the presence of probe-sample adhesive interactions, which are common especially during retraction of the rigid tip from soft materials, the Hertzian models are no longer adequate. A number of theories (e.g., Johnson-Kendall-Roberts and Derjaguin-Muller-Toporov), covering the full range of sample compliance relative to adhesive force and tip radius, are available for analysis of such data. We incorporated Pietrement and Troyon's approximation (2000, "General Equations Describing Elastic Indentation Depth and Normal Contact Stiffness Versus Load," J. Colloid Interface Sci., 226(1), pp. 166-171) of the Maugis-Dugdale model into the automated procedure. The scheme developed for the processing of Hertzian data was extended to allow for adhesive contact by applying the Pietrement-Troyon equation. Retraction force-displacement data from the indentation of polyvinyl alcohol gels were processed using the customized software. Many of the retraction curves exhibited strong adhesive interactions that were absent in extension. We compared the values of Young's modulus extracted from the retraction data to the values obtained from the extension data and from macroscopic uniaxial compression tests. Application of adhesive contact models and the automated scheme to the retraction curves yielded average values of Young's modulus close to those obtained with Hertzian models for the extension curves. The Pietrement-Troyon equation provided a good fit to the data as indicated by small values of the mean-square error. The Maugis-Dugdale theory is capable of accurately modeling adhesive contact between a rigid spherical indenter and a soft, elastic sample. Pietrement and Troyon's empirical equation greatly simplifies the theory and renders it compatible with the general automation strategies that we developed for Hertzian analysis. Our comprehensive algorithm for automated extraction of Young's moduli from AFM indentation data has been expanded to recognize the presence of either adhesive or Hertzian behavior and apply the appropriate contact model.

157 citations

Journal ArticleDOI
TL;DR: This framework is then used to address how the network elasticity becomes modified when the network cross-linking is thermoreversible in nature, changes in the stability of the network with deformation, and the effect of a variable rate of network deformation on the non-linear elastic response.
Abstract: We review the elasticity of flexible and stiff polymer networks with permanent cross-links and synthesize these results into a unifying polymer chain network model. This framework is then used to address how the network elasticity becomes modified when the network cross-linking is thermoreversible in nature, changes in the stability of the network with deformation, and the effect of a variable rate of network deformation on the non-linear elastic response. Comparisons are made between this class of simplified network models with elasticity measurements performed on flexible chain and stiff fiber networks, both with permanent and associative cross-links. Although these network models are highly idealized, they are apparently able to capture many aspects of the elastic properties of diverse real networks.

63 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The physical limits of cell migration in dense porous environments are dependent upon the available space and the deformability of the nucleus and are modulated by matrix metalloproteinases, integrins and actomyosin function.
Abstract: Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical tissue constraints. Migration rates are further governed by the capacity to degrade ECM by proteolytic enzymes, particularly matrix metalloproteinases (MMPs), and integrin- and actomyosin-mediated mechanocoupling. Yet, how these parameters cooperate when space is confined remains unclear. Using MMP-degradable collagen lattices or nondegradable substrates of varying porosity, we quantitatively identify the limits of cell migration by physical arrest. MMP-independent migration declined as linear function of pore size and with deformation of the nucleus, with arrest reached at 10% of the nuclear cross section (tumor cells, 7 µm2; T cells, 4 µm2; neutrophils, 2 µm2). Residual migration under space restriction strongly depended upon MMP-dependent ECM cleavage by enlarging matrix pore diameters, and integrin- and actomyosin-dependent force generation, which jointly propelled the nucleus. The limits of interstitial cell migration thus depend upon scaffold porosity and deformation of the nucleus, with pericellular collagenolysis and mechanocoupling as modulators.

1,140 citations

Journal ArticleDOI
TL;DR: A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.
Abstract: Osteoarthritis (OA) is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.

702 citations

Journal ArticleDOI
TL;DR: On average, YM values for soft tissues are consistently lower when obtained by indentation deformations, and the implications and potential impact of this finding are discussed.
Abstract: In this review, we compare the reported values of Young's modulus (YM) obtained from indentation and tensile deformations of soft biological tissues. When the method of deformation is ignored, YM values for any given tissue typically span several orders of magnitude. If the method of deformation is considered, then a consistent and less ambiguous result emerges. On average, YM values for soft tissues are consistently lower when obtained by indentation deformations. We discuss the implications and potential impact of this finding.

559 citations

Journal ArticleDOI
TL;DR: The poroelastic model is directly validated to explain cellular rheology at physiologically relevant timescales using microindentation tests in conjunction with mechanical, chemical and genetic treatments and shows that water redistribution through the solid phase of the cytoplasm (cytoskeleton and macromolecular crowders) plays a fundamental role in setting cellularRheology.
Abstract: The cytoplasm is the largest part of the cell by volume and hence its rheology sets the rate at which cellular shape changes can occur. Recent experimental evidence suggests that cytoplasmic rheology can be described by a poroelastic model, in which the cytoplasm is treated as a biphasic material consisting of a porous elastic solid meshwork (cytoskeleton, organelles, macromolecules) bathed in an interstitial fluid (cytosol). In this picture, the rate of cellular deformation is limited by the rate at which intracellular water can redistribute within the cytoplasm. However, direct supporting evidence for the model is lacking. Here we directly validate the poroelastic model to explain cellular rheology at physiologically relevant timescales using microindentation tests in conjunction with mechanical, chemical and genetic treatments. Our results show that water redistribution through the solid phase of the cytoplasm (cytoskeleton and macromolecular crowders) plays a fundamental role in setting cellular rheology.

545 citations