Frank Zok

Publications of Frank Zok

• The tissue diagnostic instrument.

  Authors: Paul Hansma, Hongmei Yu, David Schultz, Azucena Rodriguez, Eugene A Yurtsev, Jessica Orr, Simon Tang, Jon Miller, Joseph Wallace, Frank Zok [......] Carol Chen, Mathilde Peters, David Kohn, Jenni Buckley, Xiaojuan Li, Lisa Pruitt, Adolfo Diez-Perez, Tamara Alliston, Valerie Weaver, Jeffrey Lotz

  The Review of scientific instruments. 06/2009; 80(5):054303.

  Tissue mechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebral diskTissue mechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebral disk degeneration, cancer, atherosclerosis, osteoarthritis, osteoporosis, and tooth decay. Here we introduce the tissue diagnostic instrument (TDI), a device designed to probe the mechanical properties of normal and diseased soft and hard tissues not only in the laboratory but also in patients. The TDI can distinguish between the nucleus and the annulus of spinal disks, between young and degenerated cartilage, and between normal and cancerous mammary glands. It can quantify the elastic modulus and hardness of the wet dentin left in a cavity after excavation. It can perform an indentation test of bone tissue, quantifying the indentation depth increase and other mechanical parameters. With local anesthesia and disposable, sterile, probe assemblies, there has been neither pain nor complications in tests on patients. We anticipate that this unique device will facilitate research on many tissue systems in living organisms, including plants, leading to new insights into disease mechanisms and methods for their early detection.

• The tissue diagnostic instrument

  Authors: Paul Hansma, Hongmei Yu, David Schultz, Eugene A. Yurtsev, Jessica Orr, Simon Tang, Jon Miller, Frank Zok, Richard Souza, Alexander Proctor, Xavier Nogues-Solan, M.Jesus Peña, Lisa Pruitt, Adolfo Diez-Perez, Tamara Alliston, Valerie Weaver, Jeff Lotz

  Review of Scientific Instruments. 05/2009;

  Tissue mechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebralTissue mechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebral disk degeneration, cancer, atherosclerosis, osteoarthritis, osteoporosis, and tooth decay. Here we introduce the tissue diagnostic instrument �TDI�, a device designed to probe the mechanical properties of normal and diseased soft and hard tissues not only in the laboratory but also in patients. The TDI can distinguish between the nucleus and the annulus of spinal disks, between young and degenerated cartilage, and between normal and cancerous mammary glands. It can quantify the elastic modulus and hardness of the wet dentin left in a cavity after excavation. It can perform an indentation test of bone tissue, quantifying the indentation depth increase and other mechanical parameters. With local anesthesia and disposable, sterile, probe assemblies, there has been neither pain nor complications in tests on patients. We anticipate that this unique device will facilitate research on many tissue systems in living organisms, including plants, leading to new insights into disease mechanisms and methods for their early detection. © 2009 American Institute of Physics. �DOI: 10.1063/1.3127602� I. INTRODUCTION The tissue diagnostic instrument �TDI� was redesigned from the bone diagnostic instrument1,2 so as to measure tissue mechanical properties subcutaneously and in vivo with additional probe assemblies and an adjustable compliance �Fig. 1�. It consists of a thin probe assembly that can penetrate skin and soft tissue to reach deep tissues. The disposable, sterilizable probe assembly consists of an outer reference probe made from a 23 gauge hypodermic needle and an inner test probe made from stainless steel wire ranging from 175 to 300 �m in diameter and from 2 to 90 mm in length. Since friction between the test probe and the reference probe increases with length, it is desirable to use only the length needed to access the desired tissue location. The test probe is held in a nickel tube that couples to a magnet, which in turn is linked to a force generator. During operation the force generator oscillates the probe within the tissue of interest and concurrently measures the force and displacement. The maximum values for force and displacement are 12 N and 600 �m. The probe is typically operated at a frequency of 4 Hz because this is rapid enough to allow hand holding yet sufficiently slow to allow easy decoupling of the elastic and viscous response of the tissue �see supplementary material3 for more details including force and displacement ranges.� II. MEASUREMENTS We first illustrate TDI use in human spinal disks that are composed of a thick outer ligament �annulus fibrosus� and a central swelling hydrogel �nucleus pulposus�. Spinal disk degeneration can be the underlying cause of back pain leading to significant morbidity and societal expense. Intervertebral disks are one of the most highly loaded tissues in the body, and consequently material property insufficiency can lead to damage accumulation, inflammation, and pain. Disk degen- REVIEW OF SCIENTIFIC INSTRUMENTS 80, 054303 �2009� 0034-6748/2009/80�5�/054303/6/$25.00 80, 054303-1 © 2009 American Institute of Physics Downloaded 28 May 2009 to 72.215.163.35. Redistribution subject to AIP license or copyright; see http://rsi.aip.org/rsi/copyright.jsp

• Metals and the Integrity of a Biological Coating: The Cuticle of Mussel Byssus.

  Authors: Niels Holten-Andersen, Thomas Mates, Muhammet Toprak, Galen Stucky, Frank Zok, J Waite

  Langmuir : the ACS journal of surfaces and colloids. 11/2008;

  The cuticle of mussel byssal threads is a robust natural coating that combines high extensibility with high stiffness and hardness. In this study, fluorescence microscopy and elemental analysis wereThe cuticle of mussel byssal threads is a robust natural coating that combines high extensibility with high stiffness and hardness. In this study, fluorescence microscopy and elemental analysis were exploited to show that the 3,4-dihydroxyphenyl- l-alanine (dopa) residues of mussel foot protein-1 colocalize with Fe and Ca distributions in the cuticle of Mytilus galloprovincialis mussel byssal threads. Chelated removal of Fe and Ca from the cuticle of intact threads resulted in a 50% reduction in cuticle hardness, and thin sections subjected to the same treatment showed a disruption of cuticle integrity. Dopa-metal complexes may provide significant interactions for the integrity of composite cuticles deformed under tension.

• Jumbo squid beaks: inspiration for design of robust organic composites.

  Authors: Ali Miserez, Youli Li, J Herbert Waite, Frank Zok

  Acta biomaterialia. 02/2007; 3(1):139-49.

  The hard tissues found in some invertebrate marine organisms represent intriguing paradigms for robust, lightweight materials. The present study focuses on one such tissue: that comprising the beakThe hard tissues found in some invertebrate marine organisms represent intriguing paradigms for robust, lightweight materials. The present study focuses on one such tissue: that comprising the beak of the jumbo squid (Dosidicus gigas). Its main constituents are chitin fibers (15-20wt.%) and histidine- and glycine-rich proteins (40-45%). Notably absent are mineral phases, metals and halogens. Despite being fully organic, beak hardness and stiffness are at least twice those of the most competitive synthetic organic materials (notably engineering polymers) and comparable to those of Glycera and Nereis jaws. Furthermore, the combination of hardness and stiffness makes the beaks more resistant to plastic deformation when in contact with blunt abrasives than virtually all metals and polymers. The 3,4-dihydroxy-l-phenylalanine and abundant histidine content in the beak proteins as well as the pigmented hydrolysis-resistant residue are suggestive of aromatic cross-linking. A high cross-linking density between the proteins and chitin may be the single most important determinant of hardness and stiffness in the beak. Beak microstructure is characterized by a lamellar arrangement of the constituents, with a weak interface that promotes crack deflection and endows the structure with high fracture toughness. The susceptibility of this microstructure to cracking along these interfaces from contact stresses at the external surface is mitigated by the presence of a protective coating.

• Halogenated veneers: protein cross-linking and halogenation in the jaws of nereis, a marine polychaete worm.

  Authors: Henrik Birkedal, Rashda K Khan, Nelle Slack, Chris Broomell, Helga C Lichtenegger, Frank Zok, Galen D Stucky, J Herbert Waite

  Chembiochem : a European journal of chemical biology. 10/2006; 7(9):1392-9.

  Mineralized tissues are produced by most living organisms for load and impact functions. In contrast, the jaws of the clam worm, Nereis, are hard without mineralization. However, they are peculiarlyMineralized tissues are produced by most living organisms for load and impact functions. In contrast, the jaws of the clam worm, Nereis, are hard without mineralization. However, they are peculiarly rich in halogens, which are associated with a variety of post-translationally modified amino acids, many of which are multiply halogenated by chlorine, bromine, and/or iodine. Several of these modified amino acids, namely dibromohistidine, bromoiodohistidine, chloroiodotyrosine, bromoiodotyrosine, chlorodityrosine, chlorotrityrosine, chlorobromotrityrosine, and bromoiodotrityrosine, have not been previously reported. We have found that the distributions of Cl, Br, and I differ: Cl is widespread whereas Br and I, although not colocalized, are concentrated in proximity to the external jaw surfaces. By using nanoindentation, we show that Br and I are unlikely to play a purely mechanical role, but that the local Zn and Cl concentrations and jaw microstructure are the prime determinants of local jaw hardness. Several of the post-translationally modified amino acids are akin to those found in various sclerotized structures of invertebrates, and we propose that they are part of a cross-linked protein casing.