A computational study of liposome logic: towards cellular computing from the bottom up

Abstract

In this paper we propose a new bottom-up approach to cellular computing, in which computational chemical processes are encapsulated within liposomes. This ''liposome logic'' approach (also called vesicle computing) makes use of supra-molecular chemistry constructs, e.g. protocells, chells, etc. as minimal cellular platforms to which logical functionality can be added. Modeling and simulations feature prominently in ''top-down'' synthetic biology, particularly in the specification, design and implementation of logic circuits through bacterial genome reengineering. The second contribution in this paper is the demonstration of a novel set of tools for the specification, modelling and analysis of ''bottom-up'' liposome logic. In particular, simulation and modelling techniques are used to analyse some example liposome logic designs, ranging from relatively simple NOT gates and NAND gates to SR-Latches, D Flip-Flops all the way to 3 bit ripple counters. The approach we propose consists of specifying, by means of P systems, gene regulatory network-like systems operating inside proto-membranes. This P systems specification can be automatically translated and executed through a multiscaled pipeline composed of dissipative particle dynamics (DPD) simulator and Gillespie's stochastic simulation algorithm (SSA). Finally, model selection and analysis can be performed through a model checking phase. This is the first paper we are aware of that brings to bear formal specifications, DPD, SSA and model checking to the problem of modeling target computational functionality in protocells. Potential chemical routes for the laboratory implementation of these simulations are also discussed thus for the first time suggesting a potentially realistic physiochemical implementation for membrane computing from the bottom-up.

Steady state analysis of a vesicle bioreactor with mechanosensitive channels

“…Owing to their simple but non-linear responses, MS open new avenues within the study of synthetic biological systems (Cheng and Lu, 2012;Maharbiz, 2012). Since MS channels can help to modulate the protocell response to signals, allowing them to achieve more complex behaviors (such as alternative steady states), and MS can also be modulated, for example, by means of light activation (Folgering et al, 2004), we conjecture that MS channels can play a role in implementing computational features in simple models or liposome computation (Smaldon et al, 2010).…”

Photochromic molecular implementations of universal computation

“…chemotherapeutic agents where the drugs are cytotoxic. Targeted drug delivery using liposomes has already been shown (Gabizon et al, 2004), but the combination of liposomal logic (Smaldon et al, 2009(Smaldon et al, , 2010 and external influence via photochromic logic gates and registers could offer more complex targeting and condition reactive options.…”

Conventional Verification for Unconventional Computing: a Genetic XOR Gate Example

“…The model has been used as a basis for a specification language [13,15] and applied, among others, in unconventional computing using liposomes [2] and specifying a synthetic biology pulse generator [16].…”

“…One specific class of models and experiments related to unconventional computing, often called natural computing, is inspired by natural processes occurring in biology or produces in vitro (DNA strands) or in vivo (bacteria) experiments simulating different computational devices. A thorough account of the developments in the area can be found in [1], but we also mention some specific demonstrations of unconventional computing using liposomes [2], programmable polymers [3] and photochromic molecules [4].…”