Delineating elastic properties of kinesin linker and their sensitivity to point mutations

We analyze free energy estimators from simulation trials mimicking single-molecule pulling experiments on a neck linker of a kinesin motor. For that purpose, we have performed a version of steered molecular dynamics (SMD) calculations. The sample trajectories have been analyzed to derive distribution of work done on the system. In order to induce stretching of the linker, we have applied a constant pulling force to the molecule and allowed for a subsequent relaxation of its structure. The use of fluctuation relations (FR) relevant to non-equilibrium systems subject to thermal fluctuations allows us to assess the difference in free energy between stretched and relaxed conformations. To further understand effects of potential mutations on elastic properties of the linker, we have performed similar in silico studies on a structure formed of a polyalanine sequence (Ala-only) and on three other structures, created by substituting selected types of amino acid residues in the linker’s sequence with alanine (Ala) ones. The results of SMD simulations indicate a crucial role played by the Asparagine (Asn) and Lysine (Lys) residues in controlling stretching and relaxation properties of the linker domain of the motor

Fiber bragg gratings for medical applications and future challenges: A review

In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system

Fiber Bragg Gratings for Medical Applications and Future Challenges: A Review

[EN] In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system.This work was supported in part by INAIL (the Italian National Institute for Insurance against Accident at Work), through the BRIC (Bando ricerche in collaborazione) 2018 SENSE-RISC (Sviluppo di abiti intelligENti Sensorizzati per prevenzione e mitigazione di Rischi per la SiCurezza dei lavoratori) Project under Grant ID10/2018, in part by the UCBM (Universita Campus Bio-Medico di Roma) under the University Strategic HOPE (HOspital to the PatiEnt) Project, in part by the EU Framework Program H2020-FETPROACT-2018-01 NeuHeart Project under Grant GA 824071, by FCT/MEC (Fundacao para a Ciencia e Tecnologia) under the Projects UIDB/50008/2020 - UIDP/50008/2020, and by REACT (Development of optical fiber solutions for Rehabilitation and e-Health applications) FCT-IT-LA scientific action.Lo Presti, D.; Massaroni, C.; Leitao, CSJ.; Domingues, MDF.; Sypabekova, M.; Barrera, D.; Floris, I.... (2020). Fiber Bragg Gratings for Medical Applications and Future Challenges: A Review. IEEE Access. 8:156863-156888. https://doi.org/10.1109/ACCESS.2020.3019138S156863156888

Effects of Degeneration and Load History on Nucleus Pulposus Behavior

The nucleus pulposus (NP) plays a critical role in resisting loads placed on the spine, and therefore, the intervertebral disc. The function of the NP is to generate a hydrostatic pressure to evenly disperse the load within the disc. This ability hinges on the hydration of the disc, which is affected by age, health and even prior load history. This dissertation aims to elucidate key points about how the disc functions and reacts, both mechanically and biologically, to different sets of axial loading. We demonstrate our ability to create a degenerate disc model using trans-annular puncture in caudal rat discs and verify using viscoelastic analysis and histologic examination. Using a custom miniature fiber-optic pressure sensor, we determined the loss of pressurization in a degenerate versus a healthy disc. This compromised ability to generate an intradiscal pressure is essential, and indicates that a degenerate disc inadequately distributes the load and may lead to pain, injury and lack of function. We then investigated the influence of load history on the NP. Using a preload placed on a disc beforehand, we change the hydrated state of the disc before the exertion load is applied. The viscoelastic creep response was analyzed and showed changes due to the addition of the preload. We also directly observed this change by using the miniature pressure sensors to measure intradiscal pressure during the loading regime. To further track changes caused by the introduction of a preload, we examined the gene expression of several associated extracellular matrix proteins after loading. The results demonstrate changing gene expression contrary to the expected outcome, given the understood pressurized cellular environment. We speculate that instead of a hydrostatic pressure driven response, the tonic environment dictated genetic upregulation. Using collaborative efforts, we assessed the ability to use Pneumatic Artificial Muscles as the actuating element in a long term loading device for caudal rat discs. In conclusion, we gathered new reactions from the NP given a variety of changed states, both diseased and loaded. Our new findings will help complete the picture to fully understand how the disc functions, specifically the response of the N

New designs for bioinspired microstructures with adhesion to rough surfaces

Adhesion to substrates with surface roughness is a research field with many unsolved questions. A more thorough understanding of the underlying principles is important to develop new technologies with potential implications for instance in robotics, industrial automatization and wearable interfaces. Nature is a vast source of inspiration as animals have mastered climbing on various surfaces at high speed with several attachment and detachment events in a short time. In this work, new designs for dry adhesives inspired by natural blueprints are presented. Different strategies were explored to understand and tune adhesion on a range of substrates from smooth glass to polymers with skin-like roughness. Both the material properties and the geometry of the dry adhesives were utilized to improve adhesion strength. Three concepts are presented in this work: (i) composite structures with tunable interface, (ii) soft pressure sensitive adhesive layers, and (iii) funnel-shaped microstructures. This thesis aims for better understanding of the adhesion behavior as a function of several important factors including hold time, substrate material and roughness. The new concepts for bioinspired structures investigated in the present thesis will contribute to the development of performant, reversible adhesives for a variety of applications where surface roughness is involved.Adhäsion an rauen Oberflächen stellt immer noch ein Forschungsfeld mit vielen ungelösten Problemen dar. Um neue Technologien mit Bedeutung für beispielsweise die Robotik, industrielle Automatisierung und körpernahe Sensorik zu entwickeln, bedarf es eines tieferen Verständnisses der zugrunde liegenden Prinzipien. Hier stellt die Natur eine vielfältige Inspirationsquelle dar, da bestimmte Lebewesen in der Lage sind, auf unterschiedlichsten Untergründen zu haften. Im Rahmen dieser Arbeit werden der Natur nachempfundene Modelle und Lösungen zur Haftung vorgestellt. Zum Verständnis der Haftungsmechanismen und zur Optimierung der Hafteigenschaften auf einer Bandbreite von Substraten, von glattem Glas bis hin zu rauen, hautähnlichen Polymeroberflächen, wurden unterschiedliche Herangehensweisen untersucht. Zur Erhöhung der Haftkraft kamen sowohl Variationen in den verwendeten Materialien, als auch in der Geometrie der Haftstrukturen zum Einsatz. Drei Konzepte werden in dieser Arbeit vorgestellt: (i) Kompositstrukturen mit variablen Grenzflächen; (ii) weiche, drucksensitive Schichten und (iii) trichterförmige Mikrostrukturen. Es wird ein besseres Verständnis des Adhäsionsverhaltens in direktem Zusammenhang mit verschiedenen Struktur-, Substrat- und Messparametern angestrebt. Die in dieser Arbeit vorgestellten, neuen Konzepte für bioinspirierte Strukturen sollen zur Entwicklung performanter, reversibler Haftverbindungen für einen breiten Anwendungsbereich auf rauen Oberflächen beitragen.L’adhésion sur des surfaces rugueuses offre beaucoup de questions ouvertes aux chercheurs. Pour développer des technologies pionnières dans les domaines comme la robotique, automatisation industrielle et les capteurs portables, une connaissance plus détaillée des mécanismes gouvernant ce phénomène est nécessaire. La nature est une source d’inspiration vaste avec une multitude d’animaux possédant la capacité d’escalader diverses surfaces à grande vitesse. Cette thèse présente de nouveaux designs d’adhésifs secs inspirés par la nature. Différentes stratégies ont été explorées afin de comprendre et modifier l’adhésion sur des surfaces variées comme le verre poli ou des polymères avec une texture de surface ressemblant celle de la peau. Les propriétés des matériaux et la géométrie des structures ont été utilisées comme paramètres pour maximiser l’adhésion. Cette thèse comprend trois parties : (i) des structures composites avec interface variable, (ii) des films mous sensibles à la pression, et (iii) des structures en forme d’entonnoir. Les paramètres étudiés englobent entre outre le temps d’attente, le matériau du substrat et sa rugosité. Tous les concepts peuvent être raffinés et optimisé envers certaines applications. Les nouveaux concepts de structures inspirés par la nature présentés ci-dedans ont pour but de contribuer au développement d’adhésifs performants et réversibles pour une variété d’applications pour lesquelles la rugosité joue un important rôle.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 340929 awarded to Eduard Arzt and by the German Research Foundation (Deutsche Forschungsgemeinschaft) through the grant n. HE 7498/1-1 awarded to René Hensel