Vibrational Profiling of Brain Tumors and Cells

Nelson, Sultan L; Proctor, Dustin T; Ghasemloonia, Ahmad; Lama, Sanju; Zareinia, Kourosh; Ahn, Younghee; Al-Saiedy, Mustafa R; Green, Francis Hy; Amrein, Matthias; Sutherland, Garnette R.

doi:10.7150/thno.19172

Cited by 18 publications

(22 citation statements)

References 69 publications

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“…The distinct mechanical behaviors of classical cadherins and clustered protocadherins predicted by our simulations might also have implications for assembly and differential survival of the junctions they form in various types of tissues. Tissues and individual cell membranes do experience oscillatory motions (145)(146)(147)(148)(149), with amplitudes of up to 3 nm and characteristic timescales that can be slow (hundreds of milliseconds) (149) or fast (hundreds of microseconds) (145). These observations suggest that the junctions we simulated would be subject to periodic stretching and compression.…”

Section: Discussionmentioning

confidence: 80%

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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Section: Discussionmentioning

confidence: 80%

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

Neel

Nisler

Walujkar

et al. 2021

Preprint

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“…This might be important in the context of cell oscillations or small-scale tissue stretching (118)(119)(120)(121)(122), where classical cadherin bonds would act as molecular shock absorbers and be mechanically robust, while In turn, the larger interface achieved through overlap by PCDH proteins permits greater variation in the number and type of residues involved in the binding interface, a key determinant of strict homophilic specificity observed for clustered PCDH proteins. These observations suggest that each set of cadherins has evolved to adopt various features (13,(124)(125)(126) 1).…”

Section: Discussionmentioning

confidence: 99%

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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“…There is substantial potential for misinterpretation of data due to cell damage during the adhesion process [ 163 ]. Studies have demonstrated the effect of bacterial adhesion position distribution on the cantilever, and the effects increased when the adhesion positions were close to the cantilever’s free end [ 164 ]. The cantilever vibration due to the attached bacteria was caused not only by the mass effect but also by the bacterial cells’ stiffness.…”

Section: The Afm Oscillating Sensor Mode (Nanomotion)mentioning

confidence: 99%

“…Nanomotion’s ability to distinguish between living samples based on their propensity to adhere to a surface opens up a wide field of other applications that enable fingerprinting of different living samples according to their health status. Nanomotion was utilized to collect brain tumor vibration signals from cultured cells based on their vibration, allowing for the differentiation of various brain tumors from the normal brain based on nanomotion characteristics [ 164 ].…”

Section: The Afm Oscillating Sensor Mode (Nanomotion)mentioning

confidence: 99%

“…For all the result display methods, the focus has been on amplitude modulation characters but frequency modulation has not been analyzed for results in order to determine the characteristics of frequencies at the different stages of the measurement process, which information could have revealed a new horizon for the visualization of the results of the viability measurement process using nanomotion. Nanomotion oscillation signals can be converted into sound signals within the human hearing frequency band [ 164 ], providing novel concepts that could lead to the development of intelligent detection devices for real-time viability measurement.…”

Section: The Afm Oscillating Sensor Mode (Nanomotion)mentioning

confidence: 99%

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Living Sample Viability Measurement Methods from Traditional Assays to Nanomotion

Al-Madani

Yao

et al. 2022

Biosensors

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Living sample viability measurement is an extremely common process in medical, pharmaceutical, and biological fields, especially drug pharmacology and toxicology detection. Nowadays, there are a number of chemical, optical, and mechanical methods that have been developed in response to the growing demand for simple, rapid, accurate, and reliable real-time living sample viability assessment. In parallel, the development trend of viability measurement methods (VMMs) has increasingly shifted from traditional assays towards the innovative atomic force microscope (AFM) oscillating sensor method (referred to as nanomotion), which takes advantage of the adhesion of living samples to an oscillating surface. Herein, we provide a comprehensive review of the common VMMs, laying emphasis on their benefits and drawbacks, as well as evaluating the potential utility of VMMs. In addition, we discuss the nanomotion technique, focusing on its applications, sample attachment protocols, and result display methods. Furthermore, the challenges and future perspectives on nanomotion are commented on, mainly emphasizing scientific restrictions and development orientations.

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Vibrational Profiling of Brain Tumors and Cells

Cited by 18 publications

References 69 publications

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

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

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Living Sample Viability Measurement Methods from Traditional Assays to Nanomotion

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