Title: Biomimetic Rebuilding of Multifunctional Red Blood Cells: Modular Design Using Functional Components

Abstract

The design and synthesis of artificial materials that mimic the structures, mechanical properties, and ultimately functionalities of biological cells remains a current holy grail of materials science. Here based on a silica cell bio-replication approach, we report the design and construction of synthetic rebuilt red blood cells (RRBCs) that fully mimic the broad properties of native RBCs: size, biconcave shape, deformability, oxygen carrying capacity, long circulation time. Four successive nano-scale processing steps: RBC bioreplication, layer-by-layer polymer deposition, and precision silica etching, followed by RBC ghost membrane vesicles fusion are employed for RRBC construction. A panel of physicochemical analyses including zeta potential measurement, fluorescence microscopy, and antibody-mediated agglutination assay proved the recapitulation of RBC shape, size, and membrane structure. Flow-based deformation studies carried out in a microfluidic blood capillary model confirrned the ability of RRBCs to deform and pass through small slits and reconstitute themselves in a manner comparable to native RBCs. Circulation studies of RRBCs conducted ex-ovo in a chick embryo and in vivo in a mouse model demonstrated the requirement of both deformability and native cell membrane surface to achieve long-term circulation. To confer additional non-native functionalities to RRBCs, we developed modular procedures in which to load functional cargosmore » such as hemoglobin, drugs, magnetic nanoparticles, and ATP biosensors within the RRBC interior to enable various functions, including oxygen delivery, therapeutic drug delivery, magnetic manipulation, and toxin biosensing and detection. Taken together, RRBCs represent a class of long circulating RBC-inspired artificial hybrid materials with a broad range of potential applications.« less

Authors:

Guo, Jimin ^[1]; Agola, Jacob Ongudi ^[1]; Serda, Rita ^[1]; Franco, Stefan ^[1]; Lei, Qi ^[2]; Wang, Lu ^[1]; Minster, Joshua ^[1]; Croissant, Jonas G. ^[1]; Butler, Kimberly S.  ^[3];

• Search DOE PAGES for author "Butler, Kimberly S."
• Search DOE PAGES for ORCID "0000-0001-6045-8636"

Zhu, Wei  ^[2];

• Search DOE PAGES for author "Zhu, Wei"
• Search DOE PAGES for ORCID "0000-0003-3240-6905"

Brinker, C. Jeffrey  ^[1]

• Search DOE PAGES for author "Brinker, C. Jeffrey"
• Search DOE PAGES for ORCID "0000-0002-7145-9324"

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+ Show Author Affiliations

1. Univ. of New Mexico, Albuquerque, NM (United States)
2. South China Univ. of Technology (SCUT), Guangzhou (China)
3. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Publication Date:

Mon May 11 00:00:00 EDT 2020

Research Org.:

Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Sponsoring Org.:

USDOE National Nuclear Security Administration (NNSA)

OSTI Identifier:

1639054

Report Number(s):

SAND2020-6217J
Journal ID: ISSN 1936-0851; 686758

Grant/Contract Number:  

AC04-94AL85000

Resource Type:

Accepted Manuscript

Journal Name:

ACS Nano

Additional Journal Information:

Journal Volume: 14; Journal Issue: 7; Journal ID: ISSN 1936-0851

Publisher:

American Chemical Society (ACS)

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES