Abstract
The atomic force microscope (AFM) is emerging as a powerful tool in cell biology. Originally developed for high-resolution imaging purposes, the AFM also has unique capabilities as a nano-indenter to probe the dynamic viscoelastic material properties of living cells in culture. In particular, AFM elastography combines imaging and indentation modalities to map the spatial distribution of cell mechanical properties, which in turn reflect the structure and function of the underlying cytoskeleton. Such measurements have contributed to our understanding of cell mechanics and cell biology and appear to be sensitive to the presence of disease in individual cells. This chapter provides a background on the principles and practice of AFM elastography and reviews the literature comparing cell mechanics in normal and diseased states, making a case for the use of such measurements as disease markers. Emphasis is placed on the need for more comprehensive and detailed quantification of cell biomechanical properties beyond the current standard methods of analysis. A number of technical and practical hurdles have yet to be overcome before the method can be of clinical use. However, the future holds great promise for AFM elastography of living cells to provide novel biomechanical markers that will enhance the detection, diagnosis, and treatment of disease.
Highlights
Many physiologic and pathophysiologic processes alter the biomechanical properties of the tissues they affect
The purpose of this article is to provide a brief introduction to cell biomechanics and its relation to disease; to describe the atomic force microscope (AFM) experiment, including principles of operation and methods of data analysis; to review recent findings in the area of cell mechanics with AFM; and to identify the current limits of the technology and future developments that would enhance transfer to the basic and clinical sciences to aid in the identification of novel cell biomechanical markers that might lead to improved detection, diagnosis, and treatment of disease
We have identified many limitations when applying the standard Hertz theory, and preliminary finite element models have motivated novel experiments and yielded alternative methods of analysis that promise to increase the information that can be obtained from AFM indentation tests [91]
Summary
Many physiologic and pathophysiologic processes alter the biomechanical properties of the tissues they affect. There has been great interest in a new technique known as elastography [5], which generally refers to any imaging modality that yields information about the mechanical properties of a tissue. Based primarily on ultrasound and magnetic resonance imaging methods, elastographic techniques have demonstrated the ability to detect the size and shape of tumors [5, 6], to identify regional anatomic differences in normal tissue stiffness [5,6], to identify abnormal cardiac deformation due to coronary artery disease [7,8], and even have been implemented in a catheter system for intravascular evaluation of atherosclerotic plaques [9]. Single cell elastography using atomic force microscopy is a technique with the potential to identify such a mechanical fingerprint. The purpose of this article is to provide a brief introduction to cell biomechanics and its relation to disease; to describe the AFM experiment, including principles of operation and methods of data analysis; to review recent findings in the area of cell mechanics with AFM; and to identify the current limits of the technology and future developments that would enhance transfer to the basic and clinical sciences to aid in the identification of novel cell biomechanical markers that might lead to improved detection, diagnosis, and treatment of disease
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