Organic bioelectronics create ionic microenvironments of inflammation and infection on phospholipid polymer to elucidate molecular dynamics of C-reactive protein
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1
Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Japan
Pathophysiological responses in a tissue are characterized by dramatic changes of biomolecular activities in response to the local microenvironment. Our understanding of disease development and ability to administer critical treatment depends heavily on the amount of accurate information we can collect from the molecular tissue microenvironments at any time. To date, however, no sensing platform has been able to achieve this on molecular level. Here, an in vitro condition that mimics the progression of inflammation/infection was created to investigate how biomolecular dynamics changes in the local microenvironments. The concept underlies the use of a cell-membrane-mimetic surface, where a custom polymer mimics phosphorylcholine (PC) as an alternative receptor for the human C-reactive protein (CRP) on the eukaryotic cell-membrane (Figure 1).
The role of native form of CRP in blood circulation during the acute phase is to bind to damaged host cells or invading microbes at the site of inflammation, thus activating the complement pathway leading to clearance by professional phagocytes. To further replicate the local ionic microenvironments of a pathogenic site, a conducting polymer-based organic bioelectronic ion pump (OEIP) delivering [Ca2+] and [H+] with a well-defined, spatio-temporal control was integrated with the sensing platform (Figure 2).
Since calcium-dependent binding of CRP to the engineered PC surface models the interactions occurring between systemic CRP and cell membrane-bound CRP receptors; the biomimetic interface allows for the first time the binding constants of CRP to PC to be determined. The data reveal the local [Ca2+] and pH are essential parameters in transforming the CRP binding kinetics, indicating a hidden mechanism on site-selective activation of circulating CRP at the foci. The study reveals the local ionic microenvironment to be an essential parameter in transforming CRP binding kinetics, indicating a hidden mechanism on site-selective activation of circulating CRP in damaged tissue. At conditions promoting active binding of CRP, it is further shown that both complement component 1q (C1q) and the tissue-constructing protein fibronectin is recruited to the site in a local pH-dependent manner.
Agneta Richter-Dahlfors; Kazuhiko Ishihara
Keywords:
Biomimetic,
biosensing,
protein,
bioinerface
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Biomaterials in immune response
Citation:
Goda
T and
Miyahara
Y
(2016). Organic bioelectronics create ionic microenvironments of inflammation and infection on phospholipid polymer to elucidate molecular dynamics of C-reactive protein.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.01075
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.