Gravity plays a central role in vertebrate development and evolution. Mechanotransduction involves the tensile tethering of veins and arteries, connections between the epidermis and dermis in skin, ...tensile stress concentrations that occur at tissue interfaces, cell-cell interactions, cell-collagen fiber stress transfer in extracellular matrix and fluid shear flow. While attention in the past has been directed at understanding the myriad of biochemical players associated with mechanotransduction pathways, less attention has been focused on determining the tensile mechanical behavior of tissues in vivo. Fibroblasts sit on the surface of collagen fibers in living skin and exert a retractile force on the fibers. This retractile force pulls against the tension in collagen fibers in skin. After fibroblast-collagen fiber interactions are altered either by changes in fibroblast adhesion or after formation of cancer associated fibroblasts, and changes in cell junctions, alterations in the retractive force leads to changes in mechanotransduction. The purpose of this paper is to present a model of tensile forces that occur at the fibroblast-collagen fiber interface and how these forces are important in extracellular matrix physiology in health and disease.
Energy storage and dissipation by composite materials are important design parameters for sensors and other devices. While polymeric materials can reversibly store energy by decreased chain ...randomness (entropic loss) they fail to be able to dissipate energy effectively and ultimately fail due to fatigue and molecular chain breakage. In contrast, composite tissues, such as muscle and tendon complexes, store and dissipate energy through entropic changes in collagen (energy storage) and viscous losses (energy dissipation) by muscle fibers or through fluid flow of the interfibrillar matrix. In this paper we review the molecular basis for energy storage and dissipation by natural composite materials in an effort to aid in the development of improved substrates for sensors, implants and other commercial devices. In addition, we introduce vibrational optical coherence tomography, a new technique that can be used to follow energy storage and dissipation by composite materials without physically touching them.
The positions of charged residues in the primary sequence of amino acids comprising the molecular model of type I collagen, the major extracellular protein found in vertebrate tissues, have been ...earlier characterized by Chapman and Hardcastle Chapman, J.A., and Hardcastle, R.A. (1974). The staining pattern of collagen fibrils. II. A comparison with patterns computer-generated from the amino acid sequence. Connect. Tissue Res. 2:151-159. When the sequence of residues is packed in the quarter-staggered arrangement described originally by Hodge and Petruska Hodge, A.J., and Petruska, J.A. (1963). Recent studies with the electron microscope on ordered aggregates of the tropocollagen macromolecule. In Aspects of Protein Structure, G.N. Ramachandran (ed.) pp. 289-300. New York: Academic Press in two dimensions and in the quasi-hexagonal model of microfibrillar assembly and molecular packing structure in three dimensions detailed recently by Orgel et al. (Orgel, J.P.R.O., Miller, A., Irving, T.C., Fischetti, R.F., Hammersley, A.P., and Wess, T.J. (2001). The in situ supermolecular structure of type I collagen. Structure 9:1061-1069; Orgel, J.P.R.O., Irving, T.C., Miller, A., and Wess, T.J. (2006). Microfibrillar structure of type I collagen in situ. Proc. Natl. Acad. Sci. U.S.A. 103: 9001-9005, the common sites of charged amino acids, specifically glutamic and aspartic acid, lysine and arginine, and hydroxylysine and histidine, of type I collagen have been examined in the present study and their locations determined in relation to one another. The respective positions of these amino acid residues are notable in several features in two dimensions within a single collagen triple helix as well as in adjacent helices. There are, first, numerous sites in which the same amino acid is adjacent in each of the three collagen helices. Second, many sites exist in which two of the same amino acids and one of the same charge are adjacent in the three helices. Third, the same two or three glutamic and/or aspartic amino acids are found in close proximity to amino acids with their counterparts, aspartic and glutamic acid, respectively. Fourth, several sites occur in which the same two or three amino acids of one charge are present in close proximity to the same two or three amino acids of opposite charge (glutamic acid and lysine or arginine residues or aspartic acid and lysine or arginine residues). Fifth, there are several sites where hydroxylysine contributes charged groups in place of one of the three lysine or arginine residues common in adjacent collagen helices. The strikingly repetitive and close nature of these specific charged groups in two dimensions is even more apparent when the molecular packing structure is investigated in three dimensions. In this instance, the most recent model of Orgel et al. Orgel, J.P.R.O., Irving, T.C., Miller, A., and Wess, T.J. (2006). Microfibrillar structure of type I collagen in situ. Proc. Natl. Acad. Sci. U.S.A. 103: 9001-9005 has been correlated for the first time with the model of Landis et al. Landis, W.J., Song, M.J., Leith, A., McEwen, L., and McEwen, B. (1993). Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high voltage electron microscopic tomography and graphic image reconstruction. J. Struct. Biol. 110: 39-54 showing channels traversing molecular arrays of collagen. Here, many of the charged amino acid sites correspond to the known type I collagen hole zones defined by Hodge and Petruska Hodge, A.J., and Petruska, J.A. (1963). Recent studies with the electron microscope on ordered aggregates of the tropocollagen macromolecule. In Aspects of Protein Structure, G.N. Ramachandran (ed.) pp. 289-300. New York: Academic Press. As such, these residues present the locations highly likely to bind Ca2+ and ions in stereochemical configurations that could serve directly as nucleation centers for the subsequent growth and development of apatite crystals representing initial events in vertebrate mineralization. Based on these results, type I collagen appears to provide a molecular framework for direct formation of apatite without the necessary intervention or mediation of other molecules in extracellular matrices of vertebrate calcifying tissues.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Collagen and proteoglycans work in unison in the ECM to bear loads, store elastic energy and then dissipate excess energy to avoid tissue fatigue and premature mechanical failure. While collagen ...fibers store elastic energy by stretching the flexible regions in the triple helix, they do so by lowering their free energy through a reduction in the entropy and a decrease in charge–charge repulsion. Entropic increases occur when the load is released that drive the reversibility of the process and transmission of excess energy. Energy is dissipated by sliding of collagen fibrils by each other with the aid of decorin molecules that reside on the d and e bands of the native D repeat pattern. Fluid flow from the hydration layer associated with the decorin and collagen fibrils hydraulically dissipates energy during sliding. The deformation is reversed by osmotic forces that cause fluid to reform a hydration shell around the collagen fibrils when the loads are removed. In this paper a model is presented describing the organization of collagen fibers in the skin and cell–collagen mechanical relationships that exist based on non-invasive measurements made using vibrational optical coherence tomography. It is proposed that under external stress, collagen fibers form a tensional network in the plane of the skin. Collagen fiber tension along with forces generated by fibroblasts exerted on collagen fibers lead to an elastic modulus that is almost uniform throughout the plane of the skin. Tensile forces acting on cells and tissues may provide a baseline for stimulation of normal mechanotransduction. We hypothesize that during aging, changes in cellular metabolism, cell–collagen interactions and light and UV light exposure cause down regulation of mechanotransduction and tissue metabolism leading to tissue atrophy.
Skin cancer is an overarching label used to classify a variety of cutaneous malignancies. Surgical excision procedures are the commonly used treatments for these lesions; however, the choice to ...perform operative intervention may be influenced by other factors. Established research and literature suggest that topical treatments limit the need for surgical intervention and its commonly associated adverse effects, including infection and scarring. In addition, the growing indications for the usage of topical therapies in BCC treatment, as well as their increased availability and therapeutic options, allow for their greater applicability in the dermatology clinic. Certain topical therapies have been highlighted in research, especially those targeting basal cell carcinoma (BCC) and actinic keratosis (AK). There is also a clear correlation between cost and treatment outcomes, considering BCC's ever-growing prevalence and the proportion of excised lesions being reported as malignant. This review will discuss BCC and AK lesion criteria that result in the most successful outcomes using topical treatments, then highlight the various topical treatment options, and finally address their clinical significance moving forward.
In this pilot study, we used vibrational optical tomography (VOCT), along with machine learning, to evaluate the specificity and sensitivity of using light and audible sound to differentiate between ...normal skin and skin cancers. The results reported indicate that the use of machine learning, and the height and location of the VOCT mechanovibrational peaks, have potential for being used to noninvasively differentiate between normal skin and different cancerous lesions. VOCT data, along with machine learning, is shown to predict the differences between normal skin and different skin cancers with a sensitivity and specificity at rates between 78 and 90%. The sensitivity and specificity will be improved using a larger database and by using other AI techniques. Ultimately, VOCT data, visual inspection, and dermoscopy, in conjunction with machine learning, will be useful in telemedicine to noninvasively identify potentially malignant skin cancers in remote areas of the country where dermatologists are not readily available.
Energy storage, transmission and dissipation are important considerations of normal mechanical homeostasis. In this paper we present a new technique termed vibrational optical coherence tomography ...(VOCT) to study the anterior anatomic structures of the pig eye to better understand how energy applied to the cornea is dissipated without delamination occurring.
VOCT uses infrared light and an applied sinusoidal audible sound wave to image and measure the resonant frequency and modulus of individual macromolecular components of tissue non-invasively. We have measured the resonant frequencies and calculated the moduli of tissues in the anterior portion of the pig eye using VOCT.
While both pig and human eyes have similar resonant frequencies, they do differ in the peak amplitudes near the frequencies of 80, 120, 150 and 250 Hz. It is known that the stroma of pig cornea is much thicker than that of human corneas and these differences may explain the normalized peak height differences. The similarity of the resonant frequency peaks near 80, 120, 150 and 250 Hz of cornea, sclera and limbus suggest that the anatomically described layers in these tissues are connected into a single biomechanical unit that can store external mechanical energy and then transmit it for dissipation. Since the energy stored and dissipated is proportional to the modulus and the ability of the tissue to deform under stress, energy storage in these tissues is related to the stiffness.
It is concluded that stored energy is transmitted to the posterior segment of the eye for dissipation through the attachment with the sclera. This mechanism of energy dissipation may protect the cornea from changes in shape, curvature, and refractive power. However, ultimately, energy dissipation through thinning of the sclera may cause globe elongation observed in subjects with myopia and glaucoma.
Noninvasive measurement of the viscoelastic properties of both natural and synthetic polymers is important for the analysis of implant design and performance as well as in industrial material ...development. In this study, we used vibrational optical coherence tomography (VOCT) to compare the elastic and viscoelastic properties of silicone polymers with standard tensile stress–strain measurements. VOCT uses acoustic vibrations and infrared light to measure the resonant frequency of viscoelastic materials. The elastic modulus was calculated from the in-phase deformation of the material at fixed frequencies using an empirical calibration curve. Viscous loss was measured after pulsing the samples based on the ratio of mechanovibrational peak widths to heights. The results showed that the optimal cure time and modulus values obtained using VOCT were like those obtained using conventional tensile testing. VOCT could capture results that were comparable to conventional testing while not destroying the material, suggesting its usefulness for in vivo and in situ measurements as well as for early quality control environments during end-use application and fabrication experiments. We conclude that VOCT is a new technique that is comparable to conventional testing for noninvasively and nondestructively measuring the viscoelastic properties of polymers.
In this study, we use vibrational optical coherence tomography (VOCT) to examine the morphology and stiffness of benign and cancerous lesions. Lesion images and 3D plots of weighted displacement ...versus frequency and depth were used to compare the cellular, dermal collagen, new blood vessels, and fibrotic composition of normal skin, actinic keratoses (AK), nodular and superficial basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs), and melanomas. The results of this study suggest that benign and cancerous lesions differ based on the addition of new cells with increased resonant frequency and stiffness (80 Hz, 1.8 MPa), new blood vessel peaks (130 Hz, 4.10 MPa) that appear to be less stiff than normal blood vessels, and new fibrous tissue peaks (260 Hz, 15–17 MPa) that are present in carcinomas but not in normal skin and only partially present (80 Hz and 130 Hz only) in AKs. Results obtained by creating images based on the location of the 80 Hz, 130 Hz, and 260 Hz peaks of cancerous skin lesions suggest that the fibrous tissue appears to surround the new cells and new lesion blood vessels. The results of this study suggest that the morphology and location of the fibrous tissues in relation to the new cancer-associated cells and lesion blood vessels may provide information on the invasiveness and metastatic potential of skin cancers. The invasiveness and metastatic potential of melanomas may be a result of the cancer-associated cells laying down fibrous tissue that is used as a pathway for migration. The new cancer-associated blood vessels in the vicinity of the new cancer-associated cells may promote this migration and eventual metastasis. The ratios of peak heights 50/130 Hz and 80/130 Hz of normal cells, new lesion cells, new lesion blood vessels, and fibrotic tissue may be used as a “fingerprint” for detecting melanoma and to differentiate it from other skin cancers non-invasively using VOCT.
Cutaneous melanoma is a cancer with metastatic potential characterized by varying amounts of pigment-producing melanocytes, and it is one of the most aggressive and fatal forms of skin malignancy, ...with several hundreds of thousands of cases each year. Early detection and therapy can lead to decreased morbidity and decreased cost of therapy. In the clinic, this often translates to annual skin screenings, especially for high-risk patients, and generous use of the ABCDE (asymmetry, border irregularity, color, diameter, evolving) criteria. We have used a new technique termed vibrational optical coherence tomography (VOCT) to non-invasively differentiate between pigmented and non-pigmented melanomas in a pilot study. The VOCT results reported in this study indicate that both pigmented and non-pigmented melanomas have similar characteristics, including new 80, 130, and 250 Hz peaks. Pigmented melanomas have larger 80 Hz peaks and smaller 250 Hz peaks than non-pigmented cancers. The 80 and 250 Hz peaks can be used to quantitative characterize differences between different melanomas. In addition, infrared light penetration depths indicated that melanin in pigmented melanomas has higher packing densities than in non-pigmented lesions. Using machine learning techniques, the sensitivity and specificity of differentiating skin cancers from normal skin are shown to range from about 78% to over 90% in this pilot study. It is proposed that using AI on both lesion histopathology and mechanovibrational peak heights may provide even higher specificity and sensitivity for differentiating the metastatic potential of different melanocytic lesions.
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