Soft Tissue Bruise Injury by Blunt Impact in Human-Robot Interaction - Difference of Tolerance between Chest and Extremities

Sugiura, Ryuji; Fujikawa, Tatsuo; Nishikata, Rie; Nishimoto, Tetsuya

doi:10.23919/iccas47443.2019.8971656

Cited by 20 publications

(11 citation statements)

References 17 publications

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“…Yet, these are stretching speeds that are orders of magnitude slower than what we have used in our simulations, and thus near-equilibrium conditions may better represent the response of cadherins in these contexts. In contrast, cadherins in tissues exposed to the catastrophic impact of a bullet (> 1000 nm/ns) (116) or to bruising by an external object (> 1 nm/ns) (117) might be stretched at the speeds we have used in our simulations (0.1 nm/ns).…”

Section: Discussionmentioning

confidence: 94%

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Neel

Nisler

Walujkar

et al. 2021

Preprint

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Cadherins are a superfamily of adhesion proteins involved in a variety of biological processes that include the formation of intercellular contacts, the maintenance of tissue integrity, and the development of neuronal circuits. These transmembrane proteins are characterized by ectodomains composed of a variable number of extracellular cadherin (EC) repeats that are similar but not identical in sequence and fold. E-cadherin, along with desmoglein and desmocollin proteins, are three classical-type cadherins that have slightly curved ectodomains and engage in homophilic and heterophilic interactions through an exchange of conserved tryptophan residues in their N-terminal EC1 repeat. In contrast, clustered protocadherins are straighter than classical cadherins and interact through an antiparallel homophilic binding interface that involves overlapped EC1 to EC4 repeats. Here we present molecular dynamics simulations that model the adhesive domains of these cadherins using available crystal structures, with systems encompassing up to 2.8 million atoms. Simulations of complete classical cadherin ectodomain dimers predict a two-phased elastic response to force in which these complexes first softly unbend and then stiffen to unbind without unfolding. Simulated α, β, and γ clustered protocadherin homodimers lack a two-phased elastic response, are brittle and stiffer than classical cadherins, and exhibit complex unbinding pathways that in some cases involve transient intermediates. We propose that these distinct mechanical responses are important for function, with classical cadherin ectodomains acting as molecular shock absorbers and with stiffer clustered protocadherin ectodomains facilitating overlap that favors binding specificity over mechanical resilience. Overall, our simulations provide insights into the molecular mechanics of single cadherin dimers relevant in the formation of cellular junctions essential for tissue function.

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Section: Discussionmentioning

confidence: 94%

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Neel

Nisler

Walujkar

et al. 2021

Preprint

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“…Overall, our work provides an atomistic exploration of how three essential cadherin-based cellcell junctions respond to force as aggregate units, and how cis interactions modulate the properties of these junctions at all stages of the unbinding trajectory. While simulated timescales are short (hundreds of nanoseconds), the simulated conditions used are equivalent to those experienced by tissues exposed to blunt trauma (126,127), and we expect that our quantitative predictions from stretching simulations at fast speeds will provide upper bounds for elasticity and unbinding forces, with qualitative predictions holding even at near equilibrium conditions (103,104,110,(156)(157)(158). Future modeling efforts should focus on taking into account the effect of Ca 2+ , glycosylation, membrane, and cytoplasmic partners on the tensile and shearing mechanics of junctions that might not only include mixtures of cadherin proteins, such as classical and clustered or delta-protocadherins (159)(160)(161), but also complexes with neuroligins, nectins, and other proteins partners (97,(162)(163)(164)(165).…”

Section: Discussionmentioning

confidence: 99%

“…Adherens junctions are expected to be under tension generated by the actomyosin cytoskeleton and may experience more dramatic tensile and shearing force challenges during tissue morphogenesis and function as well as in wounding (58,(126)(127)(128)(129)(130)(131). Two similar models of adherens junction were simulated, including a first model with 24 CDH1 ectodomains (~ 3.7-M atom system) used to study the response of the junction to tensile stretching forces and a second model with 16 CDH1 ectodomains (~ 3.1-M atom system; see Materials and Methods and Table 1) used to study the response of the junction to shearing forces.…”

Section: Elastic Mechanical Response Of Adherens Junction Modelsmentioning

confidence: 99%

Collective Mechanical Responses of Cadherin-Based Adhesive Junctions as Predicted by Simulations

Neel

Nisler

Walujkar

et al. 2021

Preprint

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Cadherin-based adherens junctions and desmosomes help stabilize cell-cell contacts with additional function in mechano-signaling, while clustered protocadherin junctions are responsible for directing neuronal circuits assembly. Structural models for adherens junctions formed by epithelial cadherin (CDH1) proteins indicate that their long, curved ectodomains arrange to form a periodic, two-dimensional lattice stabilized by tip-to-tip trans interactions (across junction) and lateral cis contacts. Less is known about the exact architecture of desmosomes, but desmoglein (DSG) and desmocollin (DSC) cadherin proteins are also thought to form ordered junctions. In contrast, clustered protocadherin (PCDH) based cell-cell contacts in neuronal tissues are thought to be responsible for self-recognition and avoidance, and structural models for clustered PCDH junctions show a linear arrangement in which their long and straight ectodomains form antiparallel overlapped trans complexes. Here we report all-atom molecular dynamics simulations testing the mechanics of minimalistic adhesive junctions formed by CDH1, DSG2 coupled to DSC1, and PCDHγB4, with systems encompassing up to 3.7 million atoms. Simulations generally predict a favored shearing pathway for the adherens junction model and a two-phased elastic response to tensile forces for the adhesive adherens junction and the desmosome models. Complexes within these junctions first unbend at low tensile force and then become stiff to unbind without unfolding. However, cis interactions in both the CDH1 and DSG2-DSC1 systems dictate varied mechanical responses of individual dimers within the junctions. Conversely, the clustered protocadherin PCDHγB4 junction lacks a distinct two-phased elastic response. Instead, applied tensile force strains trans interactions directly as there is little unbending of monomers within the junction. Transient intermediates, influenced by new cis interactions, are observed after the main rupture event. We suggest that these collective, complex mechanical responses mediated by cis contacts facilitate distinct functions in robust cell-cell adhesion for classical cadherins and in self-avoidance signaling for clustered PCDHs.

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“…In this study, we performed bleeding resistance evaluation and risk curve proposal for injury occurrence, considering the flank of the specimen as a human torso. However, bleeding resistance varies across body parts (Sugiura et al, 2019). Therefore, in order to establish comprehensive safety standards for personal care robots, it is necessary to acquire data related to other body parts.…”

Section: Limitationmentioning

confidence: 99%

“…The main purpose of these studies is to collect medical findings on subcutaneous hemorrhages. Therefore, we have constructed an in vivo impact experiment method to develop these methods into resistance evaluation of subcutaneous hemorrhage (Fujikawa et al (2017b); Sugiura et al (2019)). In this report, we discuss the resistance evaluation of subcutaneous hemorrhage by the in vivo impact experiments we constructed.…”

mentioning

confidence: 99%

<i>In vivo</i> impact tests assuming human–robot contact to evaluate soft tissue bruise injury tolerance

Sugiura

Ikarashi

Suzuki

et al. 2022

Mechanical Engineering Journal

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In this study, we performed in vivo impact experiments emulating physical contact between humans and personal care robots and evaluated the conditions resulting in bruise injury due to subcutaneous hemorrhage and injury resistance. Anesthetized live pigs were used as alternate specimens, and the experiments were performed using a self-made free-fall impact tester. We investigated the existence of subcutaneous hemorrhage and performed its quantitative evaluation by hematoxylin and eosin (HE) staining of soft tissue samples at the site of the impact load. The results showed that bleeding, adopted as the indicator of bruise injury, occurred when the total energy transferred (an index of injury resistance) was 46.8 kJ/m 2 . Further, when the net energy transferred was used as the injury resistance evaluation index, the threshold value for bleeding was 30.3 kJ/m 2 . When the maximum stress was used as the injury resistance evaluation index, the threshold value for bleeding was 1.14 MPa. To investigate the possibility of adopting the injury resistance threshold of the alternate specimens obtained in this study as the injury resistance threshold of humans, we studied the capillary bleeding resistances of the test specimens experimentally. We compared these values with the capillary resistance of humans and examined the bleeding capillaries' fragility.

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Soft Tissue Bruise Injury by Blunt Impact in Human-Robot Interaction - Difference of Tolerance between Chest and Extremities

Cited by 20 publications

References 17 publications

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Collective Mechanical Responses of Cadherin-Based Adhesive Junctions as Predicted by Simulations

<i>In vivo</i> impact tests assuming human–robot contact to evaluate soft tissue bruise injury tolerance

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