Smart polymers that mimic and even surpass the functionality of natural responsive materials have been actively researched. This study explores the design and characterization of a Single-MOlecule-based material REsponsive to Shear (SMORES) for the targeted release of A1, the platelet binding domain of the blood clotting protein von Willebrand factor (VWF). Each SMORES construct employs an aptamer molecule as the flow transducer and a microparticle to sense and amplify the hydrodynamic force. Within the construct, the aptamer, ARC1172, undergoes conformational changes beyond a shear stress threshold, mimicking the shear-responsive behavior of VWF. This conformational alteration modulates the bioavailability of its target, the VWF-A1 domain, ultimately releasing it at elevated shear. Through optical tweezer-based single-molecule force measurement, ARC1172s role as a force transducer was assessed by examining its unfolding under constant pulling force. We also investigated its refolding rate as a function of force under varied relaxation periods. These analyses revealed a narrow range of threshold forces (3-7 pN) governing the transition between folded and unfolded states. We subsequently constructed the SMORES material by conjugating ARC1172 and a microbead, and immobilizing the other end of the aptamer on a substrate. Single-molecule flow experiments on immobilized SMORES constructs revealed a peak A1 domain release within a flow rate range of (40-70 μL min). A COMSOL Multiphysics model translated these flow rates to total forces of 3.10 pN-5.63 pN experienced by the aptamers, aligning with single-molecule force microscopy predictions. Evaluation under variable flow conditions showed a peak binding of A1 to the platelet glycoprotein Ib (GPIB) within the same force range, confirming released payload functionality. Building on knowledge of aptamer biomechanics, this study presents a new strategy to create shear-stimulated biomaterials based on single biomolecules.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/d4nr02715a | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
LRIG1 is a positive prognostic marker in Merkel cell carcinoma and Merkel cell carcinoma expresses epithelial stem cell markers.
Virchows Arch
December 2021
Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The cell of origin of MCC is thus far unknown and proposed cells of origin include Merkel cells, pro-/pre- or pre-B cells, epithelial stem cells, and dermal stem cells. In this study, we aimed to shed further light on the possibility that a subset of MCC tumors arise from epithelial stem cells of the skin by examining the expression of hair follicle and epidermal stem cell markers in MCC and normal human skin.
View Article and Find Full Text PDFA novel MPLKIP-variant in three Finnish patients with non-photosensitive trichothiodystrophy type 4.
Am J Med Genet A
June 2021
The Folkhaelsan Department of Medical Genetics, The Folkhaelsan Institute of Genetics and the Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
Article Synopsis
- - Trichothiodystrophy is a rare genetic disorder characterized by abnormal hair development and affects multiple body systems; this study focuses on two Finnish families with this condition.
- - The researchers identified a new mutation in the MPLKIP gene through whole-exome sequencing, confirming the diagnosis of non-photosensitive trichothiodystrophy type 4 (TTD4) in three patients.
- - This report enhances understanding of TTD4 by detailing the patients' unique physical traits and comparing their clinical features with previously documented cases.
Quantitative sensory phenotyping in chronic neuropathic pain patients treated with unilateral L4-dorsal root ganglion stimulation.
J Transl Med
October 2020
Institute of Neurophysiology, Medical Faculty Mannheim, University Heidelberg, Heidelberg, Germany.
Article Synopsis
- A study looked at a treatment called L4-DRG stimulation for patients with a painful condition called CRPS.
- The researchers tested how patients felt different sensations like pain and touch before and after 3 months of treatment.
- They found that the treatment helped reduce pain for the patients, but it did not change how they felt warmth or touch.
Lichen planus pigmentosus-inversus in a Finnish man.
J Eur Acad Dermatol Venereol
February 2019
Department of Dermatology, Allergology and Venereology, Helsinki University Central Hospital, Helsinki, Finland.
Oral Platelet-Derived Growth Factor and Vascular Endothelial Growth Factor Inhibitor Sunitinib Prevents Chronic Allograft Injury in Experimental Kidney Transplantation Model.
Transplantation
January 2016
1 Transplantation Laboratory, University of Helsinki, Helsinki, Finland. 2 Department of surgery, Oulu University Central Hospital, Oulu, Finland. 3 Transplantation and Liver Surgery Unit, Helsinki University Central Hospital, Helsinki, Finland. 4 Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Article Synopsis
- Increased expression of PDGF and VEGF is linked to chronic rejection in kidney transplants, which can lead to allograft loss.
- Sunitinib, a tyrosine kinase inhibitor, was tested in a rat model and shown to significantly reduce neointimal formation, smooth muscle cell activity, and chronic rejection signs while improving kidney function.
- The findings suggest that targeting both PDGF and VEGF with sunitinib may offer a promising new approach for preventing chronic rejection in kidney transplant patients.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!