Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins

Araujo, R.P., Petricoin, E.F, & Liotta, L.A. (2008) Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins. Journal of Theoretical Biology, 253(3), pp. 616-622.

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Abstract

Until recently, the low-abundance (LA) range of the serum proteome was an unexplored reservoir of diagnostic information. Today it is increasingly appreciated that a diagnostic goldmine of LA biomarkers resides in the blood stream in complexed association with more abundant higher molecular weight carrier proteins such as albumin and immunoglobulins. As we now look to the possibility of harvesting these LA biomarkers more efficiently through engineered nano-scale particles, mathematical approaches are needed in order to reveal the mechanisms by which blood carrier proteins act as molecular 'mops' for LA diagnostic cargo, and the functional relationships between bound LA biomarker concentrations and other variables of interest such as biomarker intravasation and clearance rates and protein half-lives in the bloodstream. Here we show, by simple mathematical modeling, how the relative abundance of large carrier proteins and their longer half-lives in the bloodstream work together to amplify the total blood concentration of these tiny biomarkers. The analysis further suggests that alterations in the production of biomarkers lead to gradual rather than immediate changes in biomarker levels in the blood circulation. The model analysis also points to the characteristics of artificial nano-particles that would render them more efficient harvesters of tumor biomarkers in the circulation, opening up possibilities for the early detection of curable disease, rather than simply better detection of advanced disease.

Impact and interest:

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4 citations in Web of Science®

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ID Code: 73611
Item Type: Journal Article
Refereed: Yes
Keywords: Biomarkers, Carrier proteins
DOI: 10.1016/j.jtbi.2008.04.009
ISSN: 1095-8541
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Mathematical Sciences
Deposited On: 09 Jul 2014 05:39
Last Modified: 14 Jul 2014 05:56

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