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Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.
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This content will become publicly available on September 1, 2025
Performance of an aptamer‐based neuropeptide Y potentiometric sensor: dependence on spacer molecule selection
Neuropeptide Y (NPY) plays a central role in a variety of emotional and physiological functions in humans, such as forming a part of the body′s response to stress and anxiety. This work compares the impact of MCH and PEG spacer molecules on the performance of a potentiometric NPY sensor. An NPY‐specific DNA aptamer with thiol termination was immobilized onto a gold electrode surface. The performance of the sensor is compared when either an MCH‐ or PEG‐based self‐assembled monolayer is formed following aptamer immobilization. Backfilling the surface with alkanethiol spacer molecules like these is key for proper conformational folding of aptamer‐target binding. Non‐specific adhesion of NPY to the MCH‐based sensor surface was observed via surface plasmon resonance (SPR), and then confirmed via potentiometry. It is then shown that PEG improves the sensor′s sensitivity to NPY compared to the surfaces with an MCH‐based SAM. We achieve the detection of picomolar range NPY levels in buffer with a sensitivity of 36.1 mV/decade for the aptamer and PEG‐based sensor surface, thus demonstrating the promise of potentiometric sensing of NPY for future wearable deployment. The sensor′s selectivity was also studied via exposure to cortisol, a different stress marker, resulting in a 13x smaller differential voltage (aptamer‐specific) response compared to that of NPY.
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- Award ID(s):
- 1936772
- PAR ID:
- 10576232
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Electroanalysis
- Volume:
- 36
- Issue:
- 9
- ISSN:
- 1040-0397
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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