• We deigned BioScape 1 , a concurrent agent-based modeling language for the stochastic simulation of complex processes in a reactive environment in 3D space. • BioScape is based on the Stochastic Pi-Calculus, and it is motivated by the need for individual based, continuous motion, and continuous space simulation in modeling complex systems. • The novel aspects BioScape, include syntactic primitives to declare the scope in space where species can move (!), diffusion rate ("), shape (#), and reaction distance, and an operational semantics that deals with the specifics of 3D locations, verifying reaction distance, and featuring random movement. • We defined a translation from BioScape to 3pi and prove its soundness with respect to the operational semantics. !"#$%&'(#!%" *+,-./01 -2"#34 Initial Conditions: 53* &3#3 #% (%67'#3#!%"35 6%&85 • Biomaterials used for implants in the human body often lead to the development of the biofilm formation which are resistant to antibiotics and the immune system. • The current state of art lies in the design and composition of the biomaterials with antimicrobial agents. • Anti-adhesive and Antibacterial Bifunctional Polymers 2 is one way to prevent biofilm growth. 6%#!93#!": 8436758; *!<'"(#!%"35 3"#!*3(#8$!35 *!%63#8$!35- =>3# *!%-(378 (3" &%? $8-'5#- • Adhesion Phase: 2 Hours (%"(5'-!%"- • Build a computational model that yields an optimal surface that has the least total number of live and dead bacteria with the highest percentage of dead bacteria. • Build computational models using BioScape for multifunctional coatings for application in biomedical systems. Figure 1:Bifunctional Polymers of Pluronic-Lysozyme Conjugate Experiment 1: Pluronic Unmodified Experiment 2: 1% Pl-Lys Experiment 3: 100% Pl-Lys • 10 8 Binding Sites in 1 cm 2 . • In Silico: We consider substrate of 100μmX100μm which has 10 4 Binding Site. • Simulation time : 1 unit of simulation time corresponds to 10 minutes of wet lab. • Rate Parameters !"#$%&"' )*+,-.,- !,-/0-1 2$3*+4/' 5/6 2$/*-&- 7408-9&4&* :7408#"%/ !;*%&;%< =4*&" >4/. >*", 5/6 ?-",%> @*A%/- :7,%0*;-B C&9*&%%/*&9 -&$ ?-"%/*-B+ !;*%&;%1 !"%3%&+ D&+E"#"% 4F G%;,&4B49H1 I=< -&$ 5/6 J%&. =6 K#++;,%/ :5%86 4F K*40%$*;-B C&9961 L&*36 4F M/4&*&9%&1 G,% I%",%/B-&$+< K*4!;-8%' 2 ?4$%B*&9 -&$ !*0#B-E4& @-&9#-9% F4/ 7408B%N !H+"%0+ $8<8$8"(8- 1. A. Compagnoni, V. Sharma, Y. Bao, P. Bidinger, L. Bioglio, E. Bonelli, M. Libera, and S. Sukhishvili. Bioscape: A modeling and simulation language for bacteria-materials interactions. In the proceedings of 3 rd International Workshop on Interactions between Computer Science and Biology (CS2Bio), 2012. 2. A. K. Muszanska, H. J. Busscher, A. Herrmann, H.C. van der Mei and W. Norde. Pluronic-lysozyme conjugates as anti- adhesive and antibacterial bifunctional polymers for surface coating. Biomaterials, 32:6333-6341, 2011. %":%!": 3"& <'#'$8 =%$@ • The modeling and simulation framework helped in identifying biological targets and biomaterials to treat biomaterials-associated infections (BAI). • In silico results are validated with the wet lab experiments. • Spatial information helped us visualize the bacterial colonization and surface construction. • In silico experiments can greatly reduce the time and cost for wet lab experiments. ABCD :,,EF1 "2( 7G& -HII+JK <1LMH/MN AAK ABCD $8-'5#- • Growth Phase: 18 Hours • Live/Dead % Bacteria and CFUs per unit in silico experiments • Summary of Wet Lab and In Silico experiments Adhesion Phase Growth Phase • Number of PEOs and Lysozymes in silico Experiment 1: Pluronic Unmodified Experiment 2: 1% Pl-Lys Experiment 3: 100% Pl-Lys [email protected], 2.0 [email protected], 1.0 Bac()@mspaceBac, stepBac, shapeBac(size, color) = ?kill().DeadBac() + !attach.LiveBac() + [email protected].(Bac() | Bac()) + mov.Bac() LiveBac()@mspaceLiveBac, stepLiveBac, shapeLiveBac(size, color) = [email protected] DeadBac()@mspaceDeadBac, stepDeadBac, shapeDeadBac(size, color) = [email protected] PEO()@mspacePEO, stepPEO, shapePEO(size, color) = ?attach() Lyso()@mspaceLyso, stepLyso, shapeLyso(size, color) = !kill() • Model interactions/behavior • Bacteria is killed by Lysozyme. • Bacteria attaches to PEO. • Bacteria multiplies. • Concurrency, Stochasticity and 3D Space • Bacteria-biomaterials interactions are highly concurrent. • Wet lab experiments are stochastic. • 3D space has 3 new attributes: shape (#), step (") and movement space (!). • Process algebra • Send/Receive Handshake (!/?) Figure 4: Reaction radius and Reaction rates Figure 2: Process Model Figure 3: 3D Space # ! "