Characterizing the effects of heparin gel stiffness on function of primary hepatocytes

Jungmok You, Su A. Park, Dong Sik Shin, Dipali Patel, Vijay Krishna Raghunathan, Mihye Kim, Christopher J Murphy, Giyoong Tae, Alexander Revzin

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

In the liver, hepatocytes are exposed to a large array of stimuli that shape hepatic phenotype. This in vivo microenvironment is lost when hepatocytes are cultured in standard cell cultureware, making it challenging to maintain hepatocyte function in vitro. Our article focused on one of the least studied inducers of the hepatic phenotype-The mechanical properties of the underlying substrate. Gel layers comprised of thiolated heparin (Hep-SH) and diacrylated poly(ethylene glycol) (PEG-DA) were formed on glass substrates via a radical mediated thiol-ene coupling reaction. The substrate stiffness varied from 10 to 110 kPa by changing the concentration of the precursor solution. ELISA analysis revealed that after 5 days, hepatocytes cultured on a softer heparin gel were synthesizing five times higher levels of albumin compared to those on a stiffer heparin gel. Immunofluorescent staining for hepatic markers, albumin and E-cadherin, confirmed that softer gels promoted better maintenance of the hepatic phenotype. Our findings point to the importance of substrate mechanical properties on hepatocyte function.

Original languageEnglish (US)
Pages (from-to)2655-2663
Number of pages9
JournalTissue Engineering - Part A
Volume19
Issue number23-24
DOIs
StatePublished - Dec 1 2013

Fingerprint

Heparin
Hepatocytes
Gels
Stiffness
Liver
Substrates
Phenotype
Polyethylene glycols
Albumins
Mechanical properties
Ethylene Glycol
Cadherins
Sulfhydryl Compounds
Glass
Enzyme-Linked Immunosorbent Assay
Maintenance
Staining and Labeling

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

You, J., Park, S. A., Shin, D. S., Patel, D., Raghunathan, V. K., Kim, M., ... Revzin, A. (2013). Characterizing the effects of heparin gel stiffness on function of primary hepatocytes. Tissue Engineering - Part A, 19(23-24), 2655-2663. https://doi.org/10.1089/ten.tea.2012.0681

Characterizing the effects of heparin gel stiffness on function of primary hepatocytes. / You, Jungmok; Park, Su A.; Shin, Dong Sik; Patel, Dipali; Raghunathan, Vijay Krishna; Kim, Mihye; Murphy, Christopher J; Tae, Giyoong; Revzin, Alexander.

In: Tissue Engineering - Part A, Vol. 19, No. 23-24, 01.12.2013, p. 2655-2663.

Research output: Contribution to journalArticle

You, J, Park, SA, Shin, DS, Patel, D, Raghunathan, VK, Kim, M, Murphy, CJ, Tae, G & Revzin, A 2013, 'Characterizing the effects of heparin gel stiffness on function of primary hepatocytes', Tissue Engineering - Part A, vol. 19, no. 23-24, pp. 2655-2663. https://doi.org/10.1089/ten.tea.2012.0681
You, Jungmok ; Park, Su A. ; Shin, Dong Sik ; Patel, Dipali ; Raghunathan, Vijay Krishna ; Kim, Mihye ; Murphy, Christopher J ; Tae, Giyoong ; Revzin, Alexander. / Characterizing the effects of heparin gel stiffness on function of primary hepatocytes. In: Tissue Engineering - Part A. 2013 ; Vol. 19, No. 23-24. pp. 2655-2663.
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