Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

Alhalhooly, Lina; Mamnoon, Babak; Kim, Jiha; Mallik, Sanku; Choi, Yongki

doi:10.18632/oncotarget.27974

Cited by 7 publications

(10 citation statements)

References 60 publications

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“…4,5 Recent studies of cellular biomechanics have demonstrated the remarkable difference in biomechanical properties (e.g., stiffness, morphology, roughness, adhesion) between cancer cells, as well as their response to the chemotherapy drugs in hypoxia. 6 In particular, cancer cells increase the expression of membrane proteins and receptors for amplifying cell-to-cell signaling and cell-to-extracellular matrix (ECM) adhesion. Thus, the distinct expression patterns and levels of plasma membrane proteins have been identified as one of the most promising biomarkers for cancer diagnosis and attractive candidates for membrane-targeted anticancer drug development and delivery.…”

Section: ■ Introductionmentioning

confidence: 99%

Single-Molecule Force Probing of RGD-Binding Integrins on Pancreatic Cancer Cells

Alhalhooly¹,

Confeld²,

Woo³

et al. 2022

ACS Appl. Mater. Interfaces

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Integrin-targeting arginine–glycine–aspartic acid (RGD)-based nanocarriers have been widely used for tumor imaging, monitoring of tumor development, and delivery of anticancer drugs. However, the thermodynamics of an RGD–integrin formation and dissociation associated with binding dynamics, affinity, and stability remains unclear. Here, we probed the binding strength of the binary complex to live pancreatic cancer cells using single-molecule binding force spectroscopy methods, in which RGD peptides were functionalized on a force probe tip through poly(ethylene glycol) (PEG)-based bifunctional linker molecules. While the density of integrin αV receptors on the cell surface varies more than twofold from cell line to cell line, the individual RGD–integrin complexes exhibited a cell type-independent, monovalent bond strength. The load-dependent bond strength of multivalent RGD–integrin interactions scaled sublinearly with increasing bond number, consistent with the noncooperative, parallel bond model. Furthermore, the multivalent bonds ruptured sequentially either by one or in multiples, and the force strength was comparable to the synchronous rupture force. Comparison of energy landscapes of the bond number revealed a substantial decrease of kinetic off-rates for multivalent bonds, along with the increased width of the potential well and the increased potential barrier height between bound and unbound states, enhancing the stability of the multivalent bonds between them.

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Section: ■ Introductionmentioning

confidence: 99%

Single-Molecule Force Probing of RGD-Binding Integrins on Pancreatic Cancer Cells

Alhalhooly¹,

Confeld²,

Woo³

et al. 2022

ACS Appl. Mater. Interfaces

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“…These results are in line with our previous study addressing that alteration in the mechanotransduction cascade of post-treated with anti-tumor agents cells that became stiffer had also a limited tendency for cell motility and restricted potential in migration [ 16 ]. Furthermore, the increased post treatment cell membrane roughness of MCF-7 cells in combination with F-actin reorganization in both static and dynamic conditions contributes also to a stiffer cell with limited cell motility as previous studies established [ 32 , 33 ]. Similar morphology of MCF-7 cells with reduced membrane ruffles, pseudopodia, and lamellipodia was detected in the study of Flamini et al, post treatment with retinoic acid, indicating a restricted migratory phenotype [ 34 ].…”

Section: Discussionmentioning

confidence: 61%

Engineering Breast Cancer Cells and hUMSCs Microenvironment in 2D and 3D Scaffolds: A Mechanical Study Approach of Stem Cells in Anticancer Therapy

2021

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Cell biomechanics plays a major role as a promising biomarker for early cancer diagnosis and prognosis. In the present study, alterations in modulus of elasticity, cell membrane roughness, and migratory potential of MCF-7 (ER+) and SKBR-3 (HER2+) cancer cells were elucidated prior to and post treatment with conditioned medium from human umbilical mesenchymal stem cells (hUMSCs-CM) during static and dynamic cell culture. Moreover, the therapeutic potency of hUMSCs-CM on cancer cell’s viability, migratory potential, and F-actin quantified intensity was addressed in 2D surfaces and 3D scaffolds. Interestingly, alterations in ER+ cancer cells showed a positive effect of treatment upon limiting cell viability, motility, and potential for migration. Moreover, increased post treatment cell stiffness indicated rigid cancer cells with confined cell movement and cytoskeletal alterations with restricted lamellipodia formation, which enhanced these results. On the contrary, the cell viability and the migratory potential were not confined post treatment with hUMSCs-CM on HER2+ cells, possibly due to their intrinsic aggressiveness. The increased post treatment cell viability and the decreased cell stiffness indicated an increased potency for cell movement. Hence, the therapy had no efficacy on HER2+ cells.

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“…Figure 1D demonstrates various applications of bio-AFM (Hoh and Hansma 1992;Shao and Yang 1995;Czajkowsky et al, 2000;Hansma 2001;Goldsbury and Scheuring 2002;Malkin et al, 2002;Alonso and Goldmann 2003;Besch et al, 2003;Gadegaard 2006;Shahin and Barrera 2008;Goldsbury et al, 2009;Ramachandran et al, 2011;Kreplak 2016;Dufrene et al, 2017;Braet and Taatjes 2018;Gao et al, 2018;Cheong et al, 2019;Nandi and Ainavarapu 2021), and we are about to summarize these in this review. Unlike the AFM imaging modes where the probe is scanned over the surface of the substrate, the cantilever tip is first approached toward the substrate until tip-sample contact happens and then retracted in AFM dynamic force spectroscopy (AFM-DFS) (Sulchek et al, 2005;Neuert et al, 2006;Thormann et al, 2006;Diezemann and Janshoff 2008;Alessandrini et al, 2012;Sengupta et al, 2014;Sluysmans et al, 2018;Ju 2019;Reiter-Scherer et al, 2019;Alhalhooly et al, 2021) and single-molecule force spectroscopy (AFM-SMFS) experiments. These two are similar methods with slight differences.…”

Section: Introductionmentioning

confidence: 99%

Biosensing, Characterization of Biosensors, and Improved Drug Delivery Approaches Using Atomic Force Microscopy: A Review

Sarkar

2022

Front. Nanotechnol.

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Since its invention, atomic force microscopy (AFM) has come forth as a powerful member of the “scanning probe microscopy” (SPM) family and an unparallel platform for high-resolution imaging and characterization for inorganic and organic samples, especially biomolecules, biosensors, proteins, DNA, and live cells. AFM characterizes any sample by measuring interaction force between the AFM cantilever tip (the probe) and the sample surface, and it is advantageous over other SPM and electron micron microscopy techniques as it can visualize and characterize samples in liquid, ambient air, and vacuum. Therefore, it permits visualization of three-dimensional surface profiles of biological specimens in the near-physiological environment without sacrificing their native structures and functions and without using laborious sample preparation protocols such as freeze-drying, staining, metal coating, staining, or labeling. Biosensors are devices comprising a biological or biologically extracted material (assimilated in a physicochemical transducer) that are utilized to yield electronic signal proportional to the specific analyte concentration. These devices utilize particular biochemical reactions moderated by isolated tissues, enzymes, organelles, and immune system for detecting chemical compounds via thermal, optical, or electrical signals. Other than performing high-resolution imaging and nanomechanical characterization (e.g., determining Young’s modulus, adhesion, and deformation) of biosensors, AFM cantilever (with a ligand functionalized tip) can be transformed into a biosensor (microcantilever-based biosensors) to probe interactions with a particular receptors of choice on live cells at a single-molecule level (using AFM-based single-molecule force spectroscopy techniques) and determine interaction forces and binding kinetics of ligand receptor interactions. Targeted drug delivery systems or vehicles composed of nanoparticles are crucial in novel therapeutics. These systems leverage the idea of targeted delivery of the drug to the desired locations to reduce side effects. AFM is becoming an extremely useful tool in figuring out the topographical and nanomechanical properties of these nanoparticles and other drug delivery carriers. AFM also helps determine binding probabilities and interaction forces of these drug delivery carriers with the targeted receptors and choose the better agent for drug delivery vehicle by introducing competitive binding. In this review, we summarize contributions made by us and other researchers so far that showcase AFM as biosensors, to characterize other sensors, to improve drug delivery approaches, and to discuss future possibilities.

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Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

Cited by 7 publications

References 60 publications

Single-Molecule Force Probing of RGD-Binding Integrins on Pancreatic Cancer Cells

Single-Molecule Force Probing of RGD-Binding Integrins on Pancreatic Cancer Cells

Engineering Breast Cancer Cells and hUMSCs Microenvironment in 2D and 3D Scaffolds: A Mechanical Study Approach of Stem Cells in Anticancer Therapy

Biosensing, Characterization of Biosensors, and Improved Drug Delivery Approaches Using Atomic Force Microscopy: A Review

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