A Mechanoelastic Glimpse on Hyaluronan-Coated Extracellular Vesicles

Paul, Debashish; Paul, Anirban; Mukherjee, Dipanjan; Saroj, Saroj; Ghosal, Manorama; Pal, Soumik; Senapati, Dulal; Chakrabarti, Jaydeb; Pal, Samir Kumar; Rakshit, Tatini

doi:10.1021/acs.jpclett.2c01629

Cited by 9 publications

(28 citation statements)

References 48 publications

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“…Equilibrium snapshots of all the cases are shown in SI Figure S1, which are similar to those reported in the previous study 17 . The equilibration in each case is confirmed by the convergence of the area per lipid of the DPPC bilayer as done in our previous work 17 . The interface between HA-water and DPPC phases is computed from the equilibrium density profiles of the molecular constituents.…”

Section: Resultssupporting

confidence: 82%

Dynamics of aqueous suspension of short Hyaluronic acid chains near DPPC bilayer

PAUL,

Chakrabarti

2024

Preprint

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The synergy between Hyaluronic acid (HA) and lipid molecules plays a crucial role in synovial fluids, cell coatings, etc. Diseased cells in cancer and arthritis, show changes in HA concentration and chain size, impacting the viscoelastic and mechanical properties of the cells. Although the solution behavior of HA is known in experiments, a molecular-level understanding of the role of HA on the dynamics at the interface of HA-water and the cellular boundary is lacking. Here we perform atomistic molecular dynamics simulation of short HA chains in explicit water solvent in presence of DPPC bilayer, relevant in pathological cases. We identify a stable interface between HA-water and the bilayer where the water molecules are in contact with the bilayer and the HA chains are located away without any direct contact. Both translation and rotation of the interfacial waters in contact with the lipid bilayer and translation of the HA chains exhibit subdiffusive behavior. The diffusive behavior sets in slightly away from the bilayer, where the diffusion coefficients of water and HA decrease monotonically with increase in HA concentration. On the contrary, the dependence on HA chain size is only marginal due to enhanced chain flexibility as their size increases.

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Section: Resultssupporting

confidence: 82%

Dynamics of aqueous suspension of short Hyaluronic acid chains near DPPC bilayer

PAUL,

Chakrabarti

2024

Preprint

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“…Differential ultracentrifugation was performed to isolate EVs from breast cancer and normal epithelial breast cells (T47D and MCF10A). 15 Dynamic light scattering (DLS), FESEM imaging, zeta potential, and atomic force microscopy (AFM) were performed with isolated EV samples to determine EV dimensions and charge (Figure 1A, Figures S1 and S2, and Table S1). The data revealed that both EVs are spherical, and the diameters of cancer EVs are smaller (55 ± 15 nm) than those of normal EVs (100 ± 19 nm).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Probing Aberrantly Glycosylated Mucin 1 in Breast Cancer Extracellular Vesicles

Saroj,

Paul,

Ali

et al. 2023

ACS Appl. Bio Mater.

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Aberrantly glycosylated mucin 1 is a critical prognostic biomarker in breast epithelial cancers. Hypoglycosylated mucin 1 coats the surface of the cancer cells, where O-glycans are predominantly linked via an N-acetylgalactosamine moiety (GalNAc). Cancer cell-derived extracellular vesicles (EVs) carry biomarkers from parent cancer cells to the recipient cells and, therefore, could potentially be leveraged for diagnostics and noninvasive disease monitoring. We devised a label-free approach for identifying glycoprotein mucin 1 overexpression on breast cancer EVs. While exploring a plethora of biochemical (enzyme-linked immunosorbent assay, flow cytometry, and SDS-PAGE) and label-free biophysical techniques (circular dichroism and infrared spectroscopy (IR)) along with multivariate analysis, we discovered that mucin 1 is significantly overexpressed in breast cancer EVs and aberrant glycosylation in mucin 1 could be critically addressed using IR and multivariate analysis targeting the GalNAc sugar. This approach emerges as a convenient and comprehensive method of distinguishing cancer EVs from normal samples and holds potential for nonintrusive breast cancer liquid biopsy screening.

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“…The issue of low and medium molecular weight HA being retained with some EV isolation protocols is further complicated by studies indicating that HA is a component of EVs obtained from synovial fluid (Mustonen et al, 2016(Mustonen et al, , 2022, mesothelial cells (Rilla et al, 2013) and cancer cells (Paul et al, 2022;Pendiuk Goncalves et al, 2023;Rilla et al, 2013). Specifically, studies have reported that HA is associated with the EV surface (Arasu et al, 2017;Pirri et al, 2022;Rilla et al, 2014).…”

Section:  Resultsmentioning

confidence: 99%

Hyaluronic acid: An overlooked extracellular vesicle contaminant

Goncalves,

Ghebosu,

Tan

et al. 2023

J of Extracellular Vesicle

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The variable presence of contaminants in extracellular vesicle (EV) samples is one of the major contributors to a lack of inter‐study reproducibility in the field. Well‐known contaminants include protein aggregates, RNA‐protein complexes and lipoproteins, which resemble EVs in shape, size and/or density. On the contrary, polysaccharides, such as hyaluronic acid (HA), have been overlooked as EV contaminants. Here, it is shown that low and medium molecular weight HA polymers are unexpectedly retained to some extent in EV fractions using two common isolation methods known for high purity: size‐exclusion chromatography and tangential flow filtration. Although these isolation techniques are capable of efficient removal of non‐EV‐associated proteins, this is not the case for HA polymers, which are partially retained in a molecular weight‐dependent manner, especially with size‐exclusion chromatography. The supramolecular structure and hydrodynamic size of HA are likely to contribute to isolation in EV fractions of filtration‐based approaches. Conversely, HA polymers were not retained with ultracentrifugation and polymer‐based precipitation methods, which are known for co‐isolating other types of contaminants. HA has a broad range of immunomodulatory effects, similar to those ascribed to various sources of EVs. Therefore, HA contaminants should be considered in future studies to avoid potential inaccurate attributions of functional effects to EVs.

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A Mechanoelastic Glimpse on Hyaluronan-Coated Extracellular Vesicles

Cited by 9 publications

References 48 publications

Dynamics of aqueous suspension of short Hyaluronic acid chains near DPPC bilayer

Dynamics of aqueous suspension of short Hyaluronic acid chains near DPPC bilayer

Probing Aberrantly Glycosylated Mucin 1 in Breast Cancer Extracellular Vesicles

Hyaluronic acid: An overlooked extracellular vesicle contaminant

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